- Home
- Conference Proceedings
- QScience Proceedings
- Conference Proceeding
Sixth International Conference on Environmental Mutagens in Human Populations
- Conference date: 26-29 Mar 2012
- Location: Qatar National Convention Center, Doha, Qatar
- Volume number: 2012
- Published: 01 March 2012
1 - 100 of 107 results
-
-
Environmental Carcinogens: Exposure and Impacts on Children’s Health
More LessAbstractEnvironmental factors play a major role in determining the health and well-being of children who comprise over one third of the world’s population. Arsenic and carcinogenic compounds in air pollution are examples that illustrate how exposure to these compounds can potentially impact children’s health. Prenatal arsenic exposure in the human population resulted in alarming gene expression changes in newborns. Class prediction algorithms identified gene expression signatures that predict arsenic exposure in a test population with about 80 percent accuracy. A highly predictive potential biomarker gene set composed of just 11 genes was identified. These genes are promising as genetic biomarkers for prenatal arsenic exposure. There is a robust prenatal response that correlates with arsenic-exposure levels that could modulate numerous biological pathways including apoptosis, cell signaling, inflammatory response, and other stress responses, and ultimately affect health status. The health impact of exposure to environmental carcinogens in air pollution during childhood was also examined. Personal monitoring of exposure and urinary metabolite excretion showed that city school children were exposed to benzene, 1,3-butadiene and PAHs at levels significantly higher than rural children, which was approximately two-fold for benzene, four-fold for 1,3-butadiene and four-fold for PAHs. The early biological effects from exposure to carcinogens were assessed from DNA damage measured as 8-OHdG and DNA strand breaks and DNA repair capacity. 8-OHdG in leukocyte DNA which was 2.5-fold higher in city school children compared with the rural school children was statistically significantly correlated with benzene exposure level. The levels of DNA strand breaks in peripheral blood samples from the city children were 1.5-fold higher than those in the rural children. Chromosome damage measured by the challenge assay was 1.7-fold higher in city children, indicating a reduction in DNA repair capacity in these children. Taken together, significantly higher levels of DNA damage believed to be the first step in development of cancer, coupled with a decreased DNA repair capacity, indicate that these children are at a higher risk of developing cancer later in life.
-
-
-
Pollutions And Health: New Challenges, New Methods
By William DabAbstractFor a while, environment could be defined as "everything except genetic". The recent scientific progress show on the contrary that most of the health impacts of environmental pollutions are mediated through genetic and epigenetic mechanisms. It is now impossible to draw an impervious barrier between these two compartments. Environment and genetic, more particularly mutagenesis, are closely linked and this creates a new form of complexity. What is in stake is the definition of a new paradigm to understand the interactions between pollutants exposures and the onset of human diseases. The new paradigm has to encompass the four preceding ones that have guided the development of scientific research in the field of environmental health. The first one was the time of 'poisons' when Pasteur, Koch and the founders of biochemistry and physiology were thinking in terms of "one pollutants for each disease". The second one was of experimental nature with the development of modern toxicology using animal, tissue or cellular models. Then the epidemiology applied to the observational study of chronic diseases in populations emerged in the 50’s. This was the beginning of the understanding of the multifactorial nature of the determinants of many diseases. Thirty years ago, the US National Academy of Sciences promoted the quantitative risk assessment paradigm. Toxicological and epidemiological knowledge could be synthesized through four formal steps: hazard identification, dose-response relationship analysis, human exposure measurement and finally risk characterization. In this presentation, we will show that for each of these steps, recent advances in research challenge the way to assess the health impact of environmental pollutions. Using examples like bisphenol A, chemical-induced obesity, chlordecone and nanoparticles, we will discuss the desirable characteristics of the fifth paradigm that must integrate many disciplines from mathematics to social sciences.
-
-
-
Traffic Related Pollutants And Their Effects On Allergic Respiratory Diseases
More LessAbstractThe prevalence and incidence of allergic respiratory diseases have increased in Europe during the last decades, as in most industrialized countries in other parts of the world. Persistent exposure to traffic related air pollution and especially particulate matter from motor vehicles has often been discussed as one of the factors responsible for this increase. It has been recently suggested by many epidemiological studies that traffic related air pollution may increase allergic symptoms and illnesses like asthma and allergic rhinitis, although for allergic sensitisation less consistent results have been found. This view seems to be supported by recent human and animal laboratory-based studies which have shown that particulate pollutants, and in particular diesel exhaust particles, can enhance allergic inflammation and induce the development of allergic immune responses. Indeed, recent in-vivo and in-vitro studies strongly suggest that diesel exhaust particles (DEP) induce pro-inflammatory products by activating their transcription. If pollutants are to be controlled in the urban environment in a cost-effective manner, it is important that the molecular targets of DEP-induced responses be elucidated. In particular, bronchial epithelial cells are the key regulators of airway inflammation, and therefore it is crucial to clarify the cellular and molecular mechanisms that are activated by DEP in these cells. Based on the available experimental and epidemiological studies, the World Health Organisation concluded cautiously that traffic related air pollution may increase the risk of allergy development and may exacerbate symptoms in particular in susceptible subgroups, although there are still many open questions.
-
-
-
Incomplete Combustion: One of the World’s Biggest Killers
More LessAbstractA growing scientific evidence base shows that exposure to the products of poor combustion, particularly small particles, is responsible for as many as 12 million premature deaths in the world annually. Most well known is the impact of people putting burning material into their mouths—incomplete combustion of tobacco—which is responsible for about half this total. Only relatively recently, however, has the full impact of other sources of incomplete combustion become documented. Based on large international reviews of the evidence coming out this year, it is estimated that outdoor air pollution, primarily combustion-related particles, is responsible for nearly 3 million premature deaths around the world. Although people have traditionally thought of outdoor pollution as an urban phenomenon, recent studies using satellites as well as ground-level monitoring show that rural outdoor air pollution is also a serious problem in many poor countries, including much of Asia. It is also now understood that the smoke from biomass and coal use for cooking in poor countries is responsible for an even greater health burden than that from general outdoor pollution. This household air pollution directly affects 40 percent of the world population. Moving to clean combustion or non-combustion energy sources could therefore have immense health benefits globally.
-
-
-
Laser Scanning Cytometry for Automation of the Micronucleus AssayIncomplete Combustion: One of the World’s Biggest Killers
More LessAbstractLaser scanning cytometry (LSC) provides a novel approach for automated scoring of micronuclei (MN) in different types of mammalian cells, serving as a biomarker of genotoxicity and mutagenicity. In this presentation I shall discuss the advances to date in measuring MN in cell lines, buccal cells and erythrocytes, describe the advantages and outline potential challenges of this distinctive approach of analysis of nuclear anomalies. The use of multiple laser wavelengths in LSC and the high dynamic range of fluorescence and absorption detection allow simultaneous measurement of multiple cellular and nuclear features such as cytoplasmic area, nuclear area, DNA content and density of nuclei and MN, protein content and density of cytoplasm as well as other features using molecular probes. This high content analysis approach allows the cells of interest to be identified (eg binucleated cells in cytokinesis-blocked cultures) and MN scored specifically in them. MN assays in cell lines (eg the CHO cell MN assay) using LSC are increasingly used in routine toxicology screening. More high-content MN assays and the expansion of MN analysis by LSC to other models (exfoliated cells, dermal cell models, etc) hold great promise for robust and exciting developments in MN assay automation as a high-content high-throughput analysis procedure
-
-
-
Statistical Issues for Instrument Validation and Inter-laboratory Comparison of Automated Systems
More LessAbstractStatistical treatment of data for human biomonitoring has greatly improved within the last decade, and the most advanced techniques have been translated from the analysis of classic epidemiologic studies to molecular epidemiology. The use of more sophisticated techniques has improved the precision of estimates in human population studies, increasing the reliability of study results. In parallel, the increased popularity of pooled analyses, created the opportunity for a deeper insight into the sources of variability. Large collaborative studies published over the last few decades have revealed that the inter-laboratory and especially the inter-scorer variation are the most important source of variability, setting this heterogeneity as a priority field to address. The recent development of automated systems for chromosome damage scoring is going to dramatically change the level of reliability of these biomarkers. Before introducing these methods, robust standardization studies have to be started, aimed at comparing automated systems in different setting and the overlapping between different company systems. During the presentation we will discuss the list of priorities for systems standardization and the most suitable study design and the statistical analyses to be implemented for addressing these priorities.
-
-
-
The MetaSystems Metafer System – Applications in Biomonitoring Studies and Measurement of Baseline Frequencies in Human Populations
More LessAbstractThe measurement of micronuclei (MN) in human peripheral blood lymphocytes is a frequently used method to assess chromosomal damage. The development and validation of the MetaSystems Metafer MNScore system for automated image analysis of MN in cytokinesis-blocked binucleated cells (BNC) offer alternative approaches beside traditional visual analysis. The application of this method was successful in research related to mutagen sensitivity phenotype in cancer risk, radiation biodosimetry and biomonitoring studies of air pollution. In biomonitoring studies, the results from a set of 885 subjects investigated by automated image analysis of MN were published between 2009 and 2011 by our laboratory. This dataset includes the subjects ranging from newborns to adults aged 65 years, as well as males and females and smokers and non-smokers. In these studies we analyzed 1,000-6,500 BNC per subjects in DAPI stained slides. The results for the effects of age, gender and smoking obtained from this set are very similar to the data obtained by visual scoring in The International Collaborative Project on Micronucleus Frequency in Human Populations. We can recommend the automated image analysis of MN using the Metafer Score system as a reliable tool for the assessment of chromosomal damage, which allows the analysis of large numbers of binucleated cells, with the additional advantage of limited subjectivity and a lack of scoring bias, and which are so critical for visual scoring.
-
-
-
Automated Image Analysis of the Human Micronucleus Cytome Assay for High Throughput Biomonitoring Studies: IMSTAR system
More LessAbstractAnalysis of micronuclei (MN) is widely used for human biomonitoring or in vitro/in vivo genotoxicity testing, and provides a sensitive and relatively easy method to assess genetic damage (Kirsch-Volders et al, 2011). The fact that baseline MN frequencies in cytokinesis-blocked (CB) lymphocytes have been shown to be a predictive biomarker for cancer risk strengthens the importance of the CBMN assay as a reliable method for human biomonitoring of early genetic effects. We showed (Kirsch-Volders and Fenech, 2001) that scoring MN frequencies in binucleated and mononucleated cells enhances the predictive capacity of the assay. However, automation of MN analysis is needed for quicker, more reliable detection while minimizing subjective judgment and scoring, and to allow multi-center cohort analysis for biomonitoring studies. Within the framework of NewGeneris, an EU project, we developed an automated image analysis system for scoring MN in human lymphocytes in collaboration with IMSTAR. The IMSTAR system is based on specific algorithms starting from the cell as a detection unit. The whole detection and scoring process are separated into two distinct steps: in the first step, the cells and nuclei are detected; then, in the second step, the MN are searched for in the detected cells. The fact that our designed software protocol started from the cell as a detection unit, and hence the identification of mono-, bi- and polynucleated cells, and MN in these different sub-populations of cells, allows the assessment of cell proliferation through nuclearity index, which is important for an efficient assessment of mitogen response and cytostasis in human biomonitoring as these are indicative of immune function and cytotoxicity (Decordier et al, 2011). Additional requirements that should be fulfilled for development of an automated MN analysis system include: a) The system should be applicable to the CBMN methodology and accurately distinguish mono, bi- and polynucleated cells; b) Well defined scoring criteria for cell type and MN (eg, Fenech et al, 2003); c) Experienced cytologists to score MN according to the HUMN criteria; d) A standardized slide preparation protocol to obtain uniformity in cell size, cell density, and reproducibility (Decordier et al, 2009); e) Validation of the automated versus manual scoring (Decordier et al, 2009, 2011). This methodology was successfully applied to study different mother-child cohorts within the EU-project NewGeneris (Vande Loock et al, 2011). Funded by the EU Integrated Project NewGeneris, (Contract No FOOD-CT-2005-016320). NewGeneris is the acronym of ‘Newborns and Genotoxic Exposure Risks’ and ECNIS stands for ‘Environmental Cancer Risk, Nutrition and Individual Susceptibility’ (FOOD-CT-2005-513943)
-
-
-
Genetic Toxicology Research in Developing Countries: Challenges and Possibilities—Egypt as an Example
By Wagida AnwarAbstractEgypt, as many other developing countries, has several environmental exposure problems. There are exposures to chemical genotoxicants and to lifestyle factors that have been linked to increased risk for cancer. Infections can be associated with cancer development when the environmental factors interact with the infection and lead to the enhancement of the carcinogenic process. Currently, there is a growing interest to genetic toxicology research, the use of different biomarkers and genetic susceptibility testing, which can contribute effectively to risk assessment. Developing countries need to co-operate with developed countries to protect human health from disease determined or influenced by factors in the environment. The national and international research policies should highlight the need to mobilize resources for human resource development, networking, improving research culture, information sharing and pragmatic use of research findings. The exchange of experience and training is the most vital issue in developing new cadres of people with skills in health research, information and communication, needed to address the challenges facing the development of genetic toxicology research and prevention programs. Organizing international meetings and training courses may enforce this field of research and help to develop co-operative research projects which deal with different exposure conditions.
-
-
-
Adverse Environmental and Health Effects from Electronics Recycling in China
By Xia HuoAbstractBackground and Objective: Electronic waste (e-waste) is an emerging environmental health issue because of its fast accumulation as well as inadequate development in recycling technology. Guiyu, a town in south China, is one of the biggest e-waste recycling centers in the world. E-waste is disassembled and recycled by locals with crude and uncontrolled methods that produce extensive environmental pollutants. The objective of this study is to provide evidence for association between risk to human health and exposure to this e-waste recycling. Methods: Heavy metals of blood were determined by graphite furnace atomic absorption spectrometry. Polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs) and Polychlorinated biphenyls (PCBs) of blood were determined by gas chromatography/mass spectrometry in the electron capture negative ionization mode. Questionnaires were used and involved examination and experiments were conducted. All data were analyzed statistically. Results: Guiyu children and/or neonates had significantly elevated blood lead (Pb), cadmium (Cd), chromium (Cr), manganese (Mn), nickel (Ni), PBDEs, PAHs and PCB, and with impairment of neurobehavioral development, temperament alterations, lower forced volume vital capacity (FVC), male neonatal AGD (Anogenital Distance) increment, damage of lymphocyte DNA and changes of antioxidant enzymes activities. Guiyu neonates showed much higher rates of adverse birth outcomes such as fetal death, low birth weight and preterm delivery. Conclusion: Our studies suggest that environmental pollution by improper e-waste process has adversely affected local health, and especially affected children and infant health and development. This kind of exposure to e-waste chemicals may cause long-term adverse outcomes for health.
-
-
-
Molecular Genetic Studies of Radiation-exposed Human Population of the Semipalatinsk Nuclear Test Site in Kazakhstan
More LessAbstractIn the Republic of Kazakhstan, during the period between 1949 and 1989, nuclear weapon testing carried out by the former Soviet Union at the Semipalatinsk Nuclear Test Site (STS) resulted in local fallout affecting the residents of East Kazakhstan. The STS has been the site for more than 450 nuclear tests, including 26 on the ground and 87 atmospheric explosions. It is estimated that there are about 500,000 A-bomb victims around STS. These individuals have been repeatedly exposed to ionizing radiation from the radioactive cloud or environmental fallout for many years. To gain insight into the health concerns of the exposed population, we carried out a molecular genetic study to estimate health risk in a three-generation (Р0,F1,F2) sample from the STS population. We previously reported a 1.8-fold increase in minisatellite mutation (MM) rate in the exposed Р0 generation. Our results indicated that the radiation exposure from the nuclear tests had caused elevated MM rates and germ-line mutations. Although the underlying mechanisms for the instability are not known, the MM are considered as originating from genomic instability induced by radiation exposure. We further investigated the influence of polymorphisms in genes on the expression of MM in three generations of the exposed and control populations and the relationship between radiation exposure and MM expression. We chose the analyses of three polymorphic DNA-repair genes (XRCC1, XRCC2 and XRCC3) and two xenobiotic detoxification genes (GSTT1 and GSTM1). It was shown that among the exposed and in comparison with the wild-type gene, the functionally active XRCC1 Arg194Trp was significantly associated with low MM and over-represented in the exposed compared with the control populations. In a similar analysis, the functionally deficient XRCC1 Arg399Glu and XRCC3 Trp241Met were associated with increased and significantly reduced MM, respectively, but these variant genes were underrepresented in the exposed population. Both GSTT1 and GSTM1 nulls were significantly associated with increased MM. In summary, our results showed the role of susceptibility genes on the expression of MM in three generations of radiation-exposed population and the complexity of gene and environment interactions on health risk assessment.
-
-
-
Role of Endocrine Disrupting Chemicals on the Occurrence of Female Reproductive Tumors in Tehran Sepideh Arbabi Bidgoli
More LessAbstractAryl Hydrocarbon Receptor (AhR) ligands are ubiquitous endocrine disrupting chemicals (EDCs) used in consumer products, diet, air and water. These chemicals are reproductive toxicants which promote tumor formation in some reproductive model systems but human data are limited. The occurrence of reproductive tumors was exponentially grown during the last three decades especially in Tehran but the underlying risk factors remained unclear. A cross-sectional case control study was conducted on the tissue and serological levels of AhR, sex steroid receptors and 120 lifestyle in relation to exposure to EDCs in 500 premenopausal women with history of endometriosis, uterine leiomyoma, breast fibroadenoma and breast cancer from 2007–2011.Differential levels of AhR, ER, PR ,AR, were determined in mentioned female reproductive tumors . Their association with lifestyle factors was also examined in different female tumors. Logistic regression was used to estimate odds ratios (ORs) and 95 percent confidence intervals (CIs), adjusting for potential risk factors. AhR overexpression in epithelial cells of premenopausal patients emphasized the susceptibility of these cells to environmental induced reproductive disorders. Living near PAHs producing factories, consumption of animal fat, abnormal weight gain, long term (>5yrs) OCP consumption, smoking, severe stress, hormonal deregulations and exposure to other sources of xenoestrogens were correlated with an increased risk of reproductive tumors which were correlated with elevated tissue levels of AhR. Adiposity and abnormal weight gain after 18 years were considered as two major background factors, which may contribute to the levels of endogenous estrogens. It seems that AhR overexpression is affected by exposure to xenoestrogens and by adiposity. Long term exposure to EDCs can increase the tissue levels of AhR and deregulate the expression pattern of sex steroid receptors and other genes in target tissues.
-
-
-
Specific Environmental Health Concerns in Thailand: Focusing on Map Ta Phut Industrial Estate
More LessAbstractThailand, one of the countries in the South-East Asia Region, is largely tropical. People who live in this sun-intense area cannot avoid risking exposure to the high concentrations of UV radiation. The incidence of skin cancer in this country is not uncommon and is found in males more than females. Over the past few decades, Thailand's dramatic economic growth brought about new environmental challenges in the once-agrarian economy. The transition of a former agricultural and mainly rural, to a modern industrialized society has confronted the country with a wide range of environmental problems including air, water and soil pollution, as well as difficulties in the management of waste and hazardous chemicals. In parallel, such modern democratic developments and increasing societal complexity have resulted in both short-term and long-term public health issues in Thailand. Among the environmental problems listed above, air pollution appears to be the main factor. Air pollution in Thailand is obviously caused by vehicles, industrial emissions and fossil fuel power plants; other sources are garbage burning, open cooking and agricultural burning practices including deliberate forest fires. The health risks from being exposed to air pollution include nausea, headache, allergic reaction, respiratory disease, heart disease and cancer. Focusing on the Map Ta Phut district, Rayong Province, where a significant industrial base of Thailand is located, Map Ta Phut Industrial Estate consists of oil refineries, coal-fired power plants, steel industries, plastic factories and other petrochemical facilities that the cumulative amount of emitted air pollution, from industrial activity, has affected the environment and those who live nearby. Map Ta Phut came to public attention when a thousand pupils and teachers at a local school in the area had to be hospitalized from inhaling toxic emissions, leading to a number of studies. Detected in the environment were beyond-safety-standard airborne cancerous toxic chemicals, and several types of carcinogenic compounds. There were findings of unusually high levels of benzene, higher genetic damage levels of red blood cells, and significant elevation of some biomarkers of oxidative stress levels in the industrial estate workers and/or nearby residents. The terrifying outcome was from studies showing the unusually high cancer rates in the area. This serious impact on the environment and people’s health, has led to public movement and at the present time, Map Ta Phut Industrial Estate is proclaimed as a Pollution Control Zone. Environment quality has to be measured regularly and the pollution has to be reduced if is too high. This improvement is now under continuous observation.
-
-
-
Population Studies for Health and Genetic Risk Assessments
By William AuAbstractChronic exposure to environmental toxic chemicals can cause DNA damage, disease and strong selection pressure on the gene pool of exposed populations. A mechanism that can link the exposure and biological consequences is DNA repair activity. Therefore, impairment of the DNA repair function can be a critical mechanism for the development of environmental health problems. In my laboratory, we have developed a Challenge assay to detect functional DNA repair deficiencies. In this assay, lymphocytes from exposed and control subjects are irradiated with X-rays or UV-light to induce DNA damage, thus challenging them to repair the damage. Abnormal repair will result in significantly elevated chromosome aberrations or DNA strand breaks in the Comet assay. Studies around the world have used the assay to indicate that excessive exposure to mutagenic and toxic substances can cause abnormal DNA repair responses. Thus, the risk for the development of health problems is increased. In studies in collaboration with Professor Bersimbaev of Kazakhstan, 3 generations of residents who have been exposed to radioactive fallouts from nuclear bomb testings were studied. The population had generation-based increase in mini-satellite instability and preferential retention of the GSTM1 null genotype. It appears that the chronic exposure to ionizing radiation has caused DNA repair defects and the alteration of the gene pool. The latter suggests that selection pressure can potentially alter the genetic makeup of the future generations. However, no clear cut evidence of such exists among exposed human populations. In summary, these studies indicate that excessive exposure to hazardous substances can cause functional alterations in the DNA repair machinery leading to increase health risk, including the possibility of alteration of gene pool in exposed population
-
-
-
Chromosome Damage and the Damage Repair Capacity in Chinese Vinyl Chloride Monomer-exposed workers
By Zhao-Lin XiaAbstractVinyl chloride monomer (CH2=CHCl, VCM) is a certain human carcinogen and it has been proved to be a multi-organ and multi-system carcinogen. The mechanism of carcinogenesis was presumed to be related to the genetic material damage induced by electrophilic metabolites of VCM. VCM is widely used in industry, 95% of vinyl chloride was polymerized to polyvinyl chloride (PVC). China is one of the important PVC production countries, and its annual production accounts for about 10% of the global production.
This study investigated the relationship between chromosome damage (Cytokinesis-block micronucleus, CBMN) induced by VCM and the cumulative exposure dose of the VCM-exposed workers. At the same time, the DNA repair capacity test based on CBMN assay was carried out to evaluate the DNA repair capacity of the workers.
188 VCM-exposed workers are the target population, and 68 workers who did not exposed to VCM are the control population for the cross-section study. The result shows that the frequencies of CBMN in the exposed group were higher than those of the control group, and there was a dose-response relationship between VCM-exposure and the frequency of MN. In additional, Based on previous prevalence study, a follow up study on 43 VCM-exposed workers, whose frequency of MN was normal in 2004, was established to explore the relationship between abnormal frequency of MN and the VCM exposure levels. Until 2010, we found that there was different frequency of MN between groups of different VCM exposure levels. The frequency of MN for group with high VCM exposure levels is significantly higher than those of group with low VCM exposure levels, and the risk is 2.28. Moreover, 66 VCM-exposed workers were followed up for 6 years with Cytokinesis-block micronucleus (CBMN) assay in 2004, 2007 and 2010 to explore the progress of genetic damage and its influencing factors. The result shows that compared with 2004, the frequency of MN significantly increased in 2007 and 2010, and the risk were 1.11 and 1.45, respectively. The abnormal frequencies of MN in 2007 and 2010 are both higher than that of 2004, and the risk were 1.15 and 2.45, respectively, which pointed that the genetic damage are increasing year by year induced by VCM. Among all the influencing factors of DNA damage, gender had the prominent effect both on the severity and progress of chromosomal damage. Female workers had higher MN rates and changes of the both MN rates than male. Therefore, the frequency of MN of peripheral blood lymphocyte can be used as an effective and sensitive biomarker for early DNA damage and follow-up under low-level VCM exposure.
The study also focused on the DNA repair capacity of 80 VCM-exposed workers and 30 workers unexposed to VCM, as well as 30 controls. We found that the 3AB index shows the rising tendency with the increasing exposure level, which pointed the VCM exposure can decrease DNA repair capacity, and further increase the chromosomal damage. The results showed that DNA repair capacity was a comprehensive indicator with great potential to detect health damage induced by VCM and damage risk of susceptible workers. Moreover, the frequencies of MN of middle and high DNA repair capacity group are both lower than that of low DNA repair capacity group, the FR is 0.74 and 0.56, respectively. There was a dose-response relationship between DNA repair capacity and the frequency of MN. It indicated that DNA repair capacity might tightly associate with chromosomal damage induced by VCM. The DNA repair capacity would be worse, and the risk of chromosomal damage induced by VCM could be higher, so the DNA repair capacity could provide scientific evidence about the risk of chromosomal damage induced by VCM so as to protect the susceptible workers.
In conclusion, VCM can induce chromosomal damage even when the exposure level is lower than the national occupational health standard in China and the VCM exposure can decrease DNA repair capacity. The level of DNA repair capacity may be an important step of the genetic damage induced by VCM. Therefore, the health education and health surveillance should be strengthened so as to protect susceptible workers and improve the quality of working life.
This work was partly supported by the National Natural Science Foundation of China (NSFC81072280),973 program of China (2011CB503801), the Shanghai Bureau of Public Health (grants 08GWD12). We thank physicians Mr. Jun LI, Shuli FENG for their help for physical examination of the workers and data collection of VCM exposure.
-
-
-
Cytogenetic Biological Dosimetry Past, Present and Future Perspectives
More LessAbstractHuman risk assessments at low doses, low dose rates and high doses following acute exposure to ionizing radiation are of prime importance in radiation protection. These issues are of continuing importance in respect of social/economic policy relating to the industrial and medical uses of ionizing radiation, and for risk assessment among people occupationally being exposed to low and/or high LET radiation, such as astronauts, pilots, stewardess and nuclear power plant workers, as well as victims of radiation accidents. Consequently, several biological assays were developed and attempts were made to investigate formation of radiation-induced chromosome aberrations and induction of genomic instability in human lymphocytes and fibroblasts. The fluorescence in situ hybridization (FISH) technique using chromosome, chromosome-arm, chromosome region, centromere and telomere-specific DNA libraries has improved the resolution of detecting all classes of radiation-induced chromosomal inter- and intra-changes. Consequently, this has increased significantly the accuracy and detection limit of biological dosimetry. Newly obtained data indicate that (a) Premature chromosome condensation assay (cell fusion assay) is a unique method to be used for immediate dose assessment at low (5cGy) as well as high doses (≥3 Gy) and can accurately discriminate between whole- and partial-body exposure in case of mass casualties and accidental over-exposure to high doses of ionizing radiation, (b) Chemically induced PCC assay has the potential to be applied for biological dosimetry (by analyzing ring-chromosomes) in cases of high doses (> 4 Gy). This assay has been further validated in combination with M-FISH to assess genomic instability of primary tumors, (c) FISH-based translocation assay has the potential to assess acute as well as chronic exposure in cases of accidental as well as occupational exposure to ionizing radiation, either immediately following exposure or retrospectively by defining accumulative effects to red bone marrows. (d) There are distinct fingerprints (such as insertions and complex translocations) for high LET radiation in comparison to low LET radiation. The importance of these findings, their applications in different scenarios of accidental and occupational over-exposure to ionizing radiations, such as Japan atomic bomb survivors, Chernobyl, Istanbul, Mayak and Techa River cohorts, and future perspectives for biological dosimetry will be discussed.
-
-
-
Pooled Analysis: A Powerful Tool for Human Population Studies
More LessAbstractThe number of epidemiological studies involving biological markers has dramatically increased over the last few years. These studies are generally small sized and this feature has called attention to the need to summarize the individual results, while waiting for the completion of larger studies, designed to answer questions that have been raised by preliminary studies. An increasingly frequent approach is the pooled analysis of published (existing) data, which seems to provide a relevant improvement over meta-analysis in molecular epidemiology studies. The presentation will address some of the methodological issues related to pooling data of biomarker studies, taking advantage of the experience accumulated by pooled analyses of data coming from large international collaborative studies such as ESCH, HUMN, HUMNxl, and ComNet. Topics that will be discussed in more detail are: data standardization, population selection and bias, statistical analysis, ethical issues.
-
-
-
Comet Assay: An Exposure Biomarker for Human Biomonitoring
By Alok DhawanAbstractA global concern on the adverse effects of chemicals to human health has led toxicologists, and in particular genetic toxicologists, to identify environmental genotoxins. The conventional method of identification involves techniques such as Ames test, chromosomal aberrations, micronucleus assay, alkaline elution assay, etc. However, these methods are cumbersome, time consuming as well as resource-intensive. During the last two decades, a state-of-the-art technique, the single cell gel electrophoresis (SCGE) /Comet assay, has gained importance as a rapid, visual and sensitive technique for qualitative and quantitative assessment of DNA damage and repair. It is a valuable technique for detection of a variety of DNA damages, which include single and double strand breaks, alkali labile sites and oxidative base damages. Comet assay can be performed on any eukaryotic and some prokaryotic cells and may be used for both in vitro and in vivo screening of geno- and anti-genotoxic potential of chemicals. Its non-invasive nature and requirement of few cells for processing has made this assay widely accepted for monitoring human genotoxicity. Its sensitivity has enabled genetic toxicologists to monitor low-level, long-term exposure to chemicals, thus predicting genetic damage at an early stage. Our studies, in the Indian population, using the alkaline Comet assay have revealed significant gender-related differences in the extent of DNA damage in lymphocytes. DNA damage was also found to vary with eating and smoking habits, age, exercise as well as occupational exposure. In vitro Comet assay studies have also been performed using human peripheral blood lymphocytes and cell lines such as MCF-7, CHO, JM-1 to assess the genotoxic potential of environmental chemicals. The versatility of the Comet assay has indeed proven it to be a Rosetta Stone in the garden of Genetic Toxicology.
-
-
-
Chemoprofiling Of Mycotoxigenic Fungi Occurring In Maize, Sorghum And Millet Grains In Africa
More LessAbstractSorghum (Sorghum bicolor (L.) Moench) and pearl millet (Pennisetum glaucum (L.) R.Br) are indigenous crops to the African continent. Apart from maize, rice and wheat, these crops are basic staple foods for many rural communities in Africa. The growth and production of these grains can be negatively affected by plant diseases caused by diverse fungal genera. The ability of Fusarium species to produce mycotoxins, including fumonisins (FUM) and moniliformin (MON), that have detrimental health effects for both humans and animals make it important to evaluate their toxin production in crops that are intended for human consumption. Fusarium species occur naturally in maize, sorghum and millet, among other grains. Potentially toxigenic species isolated from grain samples from Nigeria harboured high FUM and MON producing strains. This was confirmed by molecular identification and by chemoprofiling in in vitro grain cultures. Mycotoxin levels of Fusarium species grown on maize patty cultures were compared to levels produced on sorghum and millet patty cultures. FUM and MON profiles of 18 Fusarium proliferatum and two other Fusarium control strains, ie high producers of either one of these toxins, were analyzed. FUM (fumonisin B1, B2 and B3) were extracted with methanol/water and MON with acetonitrile/water. The mycotoxin extracts were cleaned up using strong anion exchange solid phase extraction prior to quantification by reversed-phase HPLC. Results indicated that under conducive conditions, all the strains tested produced FUM, some in relatively large quantities (11/18), ranging from 694-17421 mg/kg culture material. For 8/18 strains the MON levels were >500 mg/kg and up to 8892 mg/kg culture material. Although there are variations in the potential or ability of F. proliferatum isolates to produce either FUM or MON, these fungi can use several grains as a source for toxin production irrespective of their original hosts. This study gives insight into the potential and ability of Fusarium species, isolated from maize, sorghum and millet, to produce mycotoxins on several grain sources, which may have a marked influence on food safety and security, and the potential health risk they hold for many rural communities in Africa.
Vismer HF, Shephard GS, Imrie G, Van der Westhuizen L, Volkwyn Y, Mngqawa P
-
-
-
Regulatory Measures Of Genetic Toxicology Testing In The Local Industries Of Drug, Cosmetics, Food Additives And Environmental Pollutants
By Fouad BadrAbstractNational and international efforts to promote research and communicate knowledge into the causes and consequences of damage to the human genome aimed to inform and support measures to ensure a healthy and sustainable environment for future generations. Developed countries have realized the need to regulatory bodies (e.g. FDA, EPA, EMEA, ICH and WHO) to be responsible for approval and administration of drugs, medical devices, cosmetics , food additives and chemicals before marketing their products. Developing countries are building their economy with a focus on industrialization programs at a pace exceeding measures which counteract hazards to both human and environment. Growing na tional industries in the fields of pharmaceuticals, food and petrochemicals will definitely impose a range of hazards to the population and the environment. The challenge facing countries of the gulf region and its neighbours is the lack of a local or regional infrastructure body which focuses on promotion of research and applications of knowledge into genetic toxicology testing, risk assessment, and regulatory policy-making to protect human health and environment. For the last few years attempts by concerned scientists in the region were practiced to fill in gaps and come up with practical solutions to overcome the need for an organization with academic and legislative power to set up regulations and guidelines for the safe marketing, labelling of pharmaceuticals, cosmetics, consumer products, pesticides and chemicals. A proposal for the establishment of a Regional Center of Excellence for Environmental Mutagenesis and Carcinogenesis Research in one of the rich Gulf countries is ready for disclosure. The proposal is based on initiatives of the European safety program REACH (Registration, Evaluation, and Authorization of Chemicals), and the well established regulatory requirements of the Food and Drug Administration, European and Japanese regulatory agencies, which requires manufacturers to conduct testing to identify potential hazards to human health and to the environment, and to submit the test data to regulatory authorities.
-
-
-
Exposure To Desert Cyanobacteria May Pose A Risk To Human Health
More LessAbstractStudies on the occurrence of cyanotoxins in desert environments are relatively rare, compared with aquatic environments. Cyanobacteria are, however, important primary-producers in desert environments where they grow rapidly after seasonal rains, stabilizing and fertilizing arid habitats. As cyanobacteria can produce toxins, we tested whether desert cyanobacteria presented a risk to human health.
Cyanobacterial crust coverage was measured using random quadrats, and representative samples of cyanobacterial crust from wadis and sabkha were removed for analysis. Extracts were produced using standard methods and toxins were measured by hplc, uplc, mass spectrometry, elisa and enzyme inhibition assays.
Cyanobacterial crusts were found to cover 80 percent of the state of qatar, and up to 87 percent of the land was covered with cyanobacteria. The neurotoxic amino acids β-n-methylamino-l-alanine (bmaa) and 2,4-diaminobutyric acid (dab) were detected in the crust material. Microcystins were detected at concentrations between 3.8 and 238 ng/g crust, equivalent to between 7 and 40µg/m2. Pcr products for the mycd gene for microcystin biosythesis were detected after amplification of dna from desert crust samples. In addition, the presence of anatoxin-a(s) was inferred by acetylcholine esterase inhibition assay. Based on the concentration of microcystins detected in crust, with reference to previously published inhalation toxicity for microcystins, in combination with the amount of dust potentially inhaled by a person, the dose of microcystins could exceed a tdi value of 3ng/kg/day for an average adult.
The presence of cyanotoxins in desert crusts has important implications for human health and further studies are required to monitor desert dust storms which may contain these crusts. Furthermore, an understanding of the risks of inhaling particles containing cyanotoxins is warranted.
-
-
-
Susceptibility of Cancer among Tannery Workers Exposed to Chromium
More LessAbstractThere is inadequate evidence about the carcinogenic effect of human exposure to chromium compound. This study aimed to estimate cytogenetic and carcinogenic effects of occupational exposure to chromium in tannery workers, and comparison of the diagnostic value of urinary cytology, nuclear matrix protein (NMP) and Kontron Image Analysis System for the detection of occult bladder cancer. Methodology: The study included 38 tannery workers and 40 unexposed subjects. Cytogenetic analysis was carried out with standard procedures on heparinised venous blood leukocytes. Urine samples were tested for abnormal cells through cytopathological examination and DNA image analysis for any abnormality in the cell life cycle, in addition to NMP, a tumor marker specific for bladder cancer, to detect suspected bladder lesions. Results: Statistical analyses revealed that there was no significant difference in chromosomal aberrations and sister chromatic exchange between tannery workers and their control. But, there were significant differences between the examined groups according to the cytopathological examination of the urine samples and DNA images. In smoking tannery workers, 4C and S phase were significantly higher and 2C was significantly lower compared to those not smoking. There was no significant difference between the two groups according to NMP. The percent of positive NMP in smoking workers was higher compared to non-smokers in both groups. Conclusion: Tannery workers were at high risk for bladder pre-cancerous lesions, but, cytogenetic changes were not approved. Urinary cytology as well as NMP can provide useful excluding information, and can be used in screening for bladder cancer in the population at risk to exclude the presence of the condition, but not as a diagnostic methods.
-
-
-
Testing the Genotoxicity of Sodium Arsenate in Human Lymphocytes
More LessAbstractSodium arsenite (SA) is a compound with formula NaAsO2. It is the sodium salt of arsenous acid which was tested for its clastogenic effect alone and in combination with gamma rays on the whole blood culture and on isolated lymphocyte culture. The results showed a significant difference in the yield of aberrations induced with respect to the culture time of 48 hours. Whole blood culture showed significant increase in gaps and breaks, whereas isolated lymphocytes culture showed significant inhibition of cell cycle and 75 percent of the lymphocytes were in their first cell cycle at 72 hours. Arsenite showed co-mutagenicity with different doses of gamma rays delivered immediately or few hours after treatment of the culture with SA. The results suggest that SA also is mutagenic at the dose level used and provide support for the indispensability of whole blood culture for evaluation of the in vivo effect of any suspected mutagen. Using isolated lymphocytes appear to have problems leading to extensive cell cycle delay.
-
-
-
In Vivo Mutagenesis by UVB Irradiation: Detection and the Underlying Mechanisms
More LessAbstractHuman genome is continuously exposed to endogenous and exogenous genotoxic agents. To evaluate genotoxicity of the agents, we have developed gpt delta mice transgenic gene mutation assay, which allows detection of mutations in vivo in any organ of mice. The mice have been established by microinjection of lambda EG10 phage DNA into fertilized eggs of C57Bl/6J mice. A feature of the transgenic mice assay is incorporation of two selections to detect different types of mutations, i.e., point mutations such as base substitutions and frameshifts by gpt or 6-thioguanine selection and deletion mutations by Spi- (sensitive to P2 interference) selection. The gpt assay effectively detects point mutations induced by a variety of chemical agents that induce DNA adducts while Spi- assay exclusively detects deletions with the molecular sizes from 1 base pair (bp) to several kilo bps (kb). We report that UVB irradiation induces base substitutions and deletions in the epidermis of gpt delta mice and also that p53 suppresses the deletions and complex mutations in vivo. The mice were exposed to UVB at single doses of 0.3, 0.5, 1.0, 1.5 and 2.0 kJ/m2. At four weeks after irradiation, mutations in the epidermis were analyzed. The UVB irradiation induced G:C to A:T mutations at dipyrimidine sites, such as 5’-TC-3’ and 5’-CC-3’. Tandem transitions such as CC to TT were also observed. In addition to point mutations, UVB induced deletions with the size of more than 1 kb. More than half of the large deletions occurred between short homologous sequences from 1 to 6 bps while others had flush ends. The results suggest that the deletions are generated by end-joining of double-strand breaks in DNA. To examine protective roles of p53 against UVB-induced mutagenesis, mutations were measured in the epidermis of UVB-induced p53+/+ and p53-/- gpt delta mice. The mice were exposed to UVB at single doses of 0.5, 1.0 and 2.0 kJ/m2, and the mutant frequencies (MF) were determined in the epidermis 4 weeks after the irradiation. Although UVB enhanced gpt MF more than 10 times over the unirradiated mice, there were no significant differences in gpt MF and the mutation spectra between p53+/+ and p53-/- mice. In contrast, the frequency of Spi- large deletions of more than 1 kb and complex mutations were significantly higher in unirradiated p53-/- mice than in unirradiated p53+/+ mice. These large deletions and complex mutations increased in a UVB-dose-dependent manner in p53+/+ mice, while no increase was observed in p53-/- mice. These results suggest that p53 does not suppress point mutations induced by UVB but suppresses large deletions and complex mutations in vivo.
-
-
-
Genotoxicity Induced By Nanomaterials
More LessAbstractNanomaterials are useful for their characteristic properties and are commonly used in various fields. The assessment of genotoxicity and safety of nanomaterials are, therefore, of serious concern. So far, we have examined genotoxic effects of various nanomaterials, including fullerenes, kaolins, multi-wall carbon nanotubes and magnetite, using in vitro and in vivo assay systems. All of these nanomaterials significantly induced micronuclei and enhanced frequency of sister chromatid exchange in cultured mammalian cells. When ICR mice were intratracheally instilled with a single dose (0.2 mg/animal) of these nanomaterials, DNA damage of the lungs analyzed by Comet assay increased about two to three times that of the vehicle control. We also analyzed the formation of DNA adducts related to oxidative stress (8-oxo-2’-deoxyguanosine and heptanone etheno-deoxyribonucleosides) in lungs of mice exposed to nanomaterials using the stable-isotope dilution LC-MS/MS method. These DNA adduct levels were increased in the nanomaterial-treated mice compared with a vehicle control. Moreover, we examined in vivo mutagenicity of nanomaterials using gpt delta transgenic mice intratracheally-instilled with four consecutive doses of 0.2 mg per animal. All nanomaterials increased gpt mutant frequencies in the lungs of gpt delta transgenic mice. Mutation spectra analysis showed transversions were predominant, and among these, the G:C to C:G was commonly increased by these nanomaterials. Based on these observations, it is suggested that oxidative stress and inflammatory responses are probably involved in the genotoxicity induced by nanomaterials. To further clarify the mechanisms of genotoxicity by nanomaterials, comprehensive DNA adduct analysis (DNA adductome) is now being investigated for DNA samples derived from lungs of mice exposed to nanomaterials. On the other hand, the effects of atypical nanomaterials such as difference of surface structure on genotoxicity are not fully elucidated yet. In the present study, we investigated the DNA damaging potency of two types of kaolins by Comet assay, and found out that genotoxicity differs between two types of kaolins. We are now investigating the incorporation rate into mammalian cells, and reactive oxygen species generation of these kaolins.
-
-
-
Basic Mechanisms in Spontaneous and Induced Mutagenesis
More LessAbstractLiving cells possess a panel of specialized DNA polymerases that deal with the large diversity of DNA lesions that occur in their genomes. How specialized DNA polymerases gain access to the replication intermediate in the vicinity of the lesion is unknown. Using a model system in which a single replication-blocking lesion can be bypassed concurrently by two pathways that leave distinct molecular signatures, we analyzed the complex interplay among replicative and specialized DNA polymerases. In Escherichia coli, the DNA damage response entails several processes such as stalling of the replication fork, activation of the SOS response and induction of dNTP synthesis. Following UV-irradiation, the ribonucleotide reductase (RNR) NrdAB that catalyzes the limiting step in dNTP synthesis, is up-regulated, leading to an increase in dNTP levels. In the present study, we investigate the effect of increased dNTP levels on the process of translesion synthesis (TLS) under DNA damage conditions. We present direct evidence that an elevated dNTP pool level facilitates translesion synthesis (TLS). TLS is a two-step mechanism involving the insertion of a nucleotide opposite the lesion and the subsequent extension steps. Although Pol III, the replicative DNA polymerase, can insert a nucleotide across certain lesion, its proofreading activity usually recognizes the inserted base across the lesion site as a mispair and removes it, thus preventing the subsequent extension steps. Our results suggest that high dNTP levels bolster the polymerase activity of Pol III, in turn reducing its exonuclease activity. The shift in the equilibrium from the exonuclease activity towards the polymerase activity of Pol III favors the production of a key TLS intermediate, ie the intermediate that contains a base inserted across from the lesion site. This intermediate is subsequently elongated by the specialized TLS polymerases. In support of the hypothesis of proofreading activity attenuation of Pol III, we show a robust increase in spontaneous mutagenesis under conditions of elevated dNTP levels referred to as the spontaneous dNTP mutator phenotype.
-
-
-
Mechanisms of Liver Carcinogenesis: Studies of Co-morbidity Factors Using Animal Models
By Ivan RusynAbstractHepatocellular carcinoma (HCC) is the most common type of primary malignancy in the liver. Main risk factors of HCC are well-defined and include hepatitis B virus (HBV); lifestyle, diet and environmental factors (e.g., alcoholic beverages, aflatoxin B1 (AFB1), and tobacco smoking); and metabolic diseases (e.g., obesity, diabetes and non-alcoholic steatohepatitis). Importantly, the rise in incidence of HCC in the developed countries has been attributed, at least in part, to an increase in hepatitis C virus (HCV) infections and non-alcoholic steatohepatitis, pathological states whose prevalence is growing in the US and Europe. In addition, liver fibrosis and cirrhosis are well known precursor liver disease states for hepatocellular HCC in humans. While animal model studies of HCC have contributed much of the understanding of the molecular events leading to disease initiation, progression and promotion, few publications examined co-morbidity factors that are known to contribute to HCC in humans. This presentation will describe two examples of experimental animal models of HCC where co-morbidity factors (HCV+AFB1, or genotoxic carcinogen diethylnitrosamine+liver fibrosis) were explored. These studies afford an opportunity to examine the molecular mechanisms that are crucial for the synergy between co-morbidity factors.
-
-
-
Low-Dose Carcinogenicity Studies and Mechanisms
More LessAbstractOne of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only four low-dose carcinogenicity studies and five low-dose biomarker/pre-neoplastic studies have been performed. The four carcinogenicity studies involved exposures of 24,192 mice to two acetylaminofluorene, 4,080 rats to nitrosamines (NDMA and NDEA), 40,000 rainbow trout to dibenz[a,l]pyrene, and 20,00 trout to aflatoxin B1. The low-dose biomarker/pre-neoplastic studies involved exposure of 1,145 rats to MeIQx, 2,000 rats each to DEN or DMN, 1,920 rats to PhIP, and 50 rats to potassium bromate. In most cases there was some evidence for a threshold effect for the induction of cancer or biomarkers of cancer. However, absolute proof of a threshold effect for carcinogenicty could not be demonstrated unambiguously by any of the carcinogenicity studies due to the limited number of animals used. The induction of stable DNA adducts was not predictive of tumors in the mouse and trout studies. All of the biomarkers evaluated, including stable DNA adducts, oxidative damage, mutation, and pre-neoplastic foci, exhibited threshold effects, ie, they were not inducible or detectable at the lowest doses tested. Clear proof of a threshold effect for any of the carcinogens tested is lacking. However, the limited data available suggest that these carcinogens may exhibit threshold effects for the induction of carcinogenic biomarkers and cancer. Given the fact that some mutagens clearly show threshold effects and that cancer is a multi-step process, it is possible that carcinogens may also show a threshold effect.
-
-
-
Environmental Toxicogenomics: How Genomic Technologies are Impacting the Science of Toxicology
More LessAbstractDecision-makers in safety assessment of exposures to environmental stressors and health care providers need improved biomarkers of toxic exposures and biomarkers of adverse events that precede the development of overt injury or disease. Two toxicogenomic studies will be presented that demonstrate the utility of genomic approaches for developing potential biomarkers of toxicity for both nephrotoxicity and hepatotoxicity. The use of calcineurin inhibitor (CI) immunosuppressants has revolutionized the clinical practice of organ transplantation. However, chronic nephrotoxicity limits their long-term utility. In order to understand the pathophysiology that underlies the development of CI-associated nephrotoxicity and to develop CI-specific biomarkers of toxicity, rats were dosed with cyclosporine A (CsA) or FK506, or rapamycin, and gene expression profiling was performed on RNA isolated from kidneys 24 hours after one, seven, 14 or 28 daily doses. A gene expression signature was identified that was correlated with CI-specific kidney damage and responded with an earlier onset than the more general kidney injury biomarkers Kim-1 and Clusterin, and is CI-specific. We have been interested in gene expression patterns derived from peripheral blood cells as they would provide useful early indicators of acute toxicity. With respect to hepatotoxicity, the case of acetaminophen (APAP) intoxication is particularly important, as this is the leading cause of liver failure in the United States. We generated a blood gene expression data set from rats exposed to APAP to train genomic classifiers of toxicity. Prediction accuracy was tested on a blinded, independent rat blood test data set and ranged from 88.9% to 95.8%. Genomic markers outperformed predictions based on traditional clinical parameters. We are currently testing the hypothesis that gene expression data from peripheral blood cells can provide valuable information about hepatotoxicity to humans, well before liver damage is detected by classical parameters. Our results support the potential use of genomic markers in the blood as surrogates for clinical markers of potential acute liver damage.
-
-
-
Genetic, Genomic and Proteomic Approaches to Identify Arsenic Susceptibility and Carcinogenicity
More LessAbstractIn West Bengal, India, more that 26 million people are exposed to arsenic through drinking water. However, only less than 15% to 20% of them show arsenic-induced skin lesions. Hence it is assumed that genetic variations might play an important role in arsenic-induced toxicity and carcinogenicity. Major genetic, genomic and proteomic approaches have been made to find out the cause of arsenic susceptibility. For this reason, the Chromosomal Aberrations (CA), Comet assay and challenge assay were performed and single nucleotide polymorphisms (SNPs) studies were carried out for a number of genes that may involve the different pathways in arsenic metabolism and detoxification SNPs of p53 gene, PNP, ERCC2 and XRCC3 genes were also analyses. Attempts have also been made to identify the different proteins in the plasma of the individuals exposed to arsenic that may be responsible for arsenic susceptibility. Individuals with p53 codon 72 Arg/Arg genotype are overrepresented, indicating that this genotype is more susceptible to arsenic-induced toxicity. Lys/Lys genotype in the ERCC2 polymorphism was almost five fold overrepresented in the arsenic-induced hyperkeratosis skin lesions group when compared to the group with no skin lesions. In each of these cases, individuals with risk genotype were found to have significantly higher genetic damage, functionally validating our associations. In case of XRCC3 T241M polymorphism, presence of at least one M allele (M/M or T/M) was protective toward development of arsenic-induced skin lesions, and also toward arsenic-related peripheral neuropathy and conjunctivitis. A significant correlation was observed between protective genotype and decreased frequencies of chromosomal aberrations. Results of DNA repair studies through Challenge and Comet assay show that the individuals with arsenic-induced skin lesions have suboptimal DNA repair capacity and are hence inefficient in combating the DNA damage induced by chronic arsenic exposure. Thus the above results indicate that the suboptimal DNA repair and genetic variations are responsible for arsenic induced toxicity and carcinogenicity. Attempts were made to identify the proteins that are differentially expressed in the arsenic unexposed and arsenic exposed skin symptomatic and asymptomatic individuals through iTraq. A number of proteins were found to be differentially expressed between exposed individuals with and without arsenic-induced skin lesions and might thus play a critical role in arsenic susceptibility.
-
-
-
Genomic Approach for Understanding the Mutagenic and Carcinogenic Mechanisms of Heavy Metal Nickel in terms of Gene-environment Interaction.
By Young R SeoAbstractNickel is a toxic metal that causes mutagenesis and promotes carcinogenesis. Its toxicological properties are partially related to the generation of reactive oxygen species (ROS) that can induce DNA damage and mutation. It also interfere redox-sensitive transcription factors, particularly p53 and hypoxia-inducible factor 1 (HIF-1), which might lead to genomic expression change. Nuclear factor erythroid-2 related factor 2 (Nrf2) is a redox factor which is responsible for control of oxidation/reduction status and consequent cytoprotection against environmental toxicants. First, we confirmed the protective effect of the Nrf2 gene under oxidative stress and DNA damage induced by 20uM nickel at sub-lethal doses in terms of gene-environment interactions. Here, we attempted to identify potential nickel and Nrf2-responsive targets and the relevant pathway via microarray, qRT-PCR, and pathway analysis. Under nickel exposure conditions, we detected significantly higher amounts of DNA damage via a comet assay, in addition to increased intracellular ROS generation, in Nrf2 lacking cells in comparison to Nrf2 wild-type cells. Additionally, gene expression data were analyzed via microarray assays for the selection of Nrf2-responsive genes under nickel treatment. In particular, altered expressions of 10 genes (CAV1, FOSL2, MICA, PIM2, RUNX1, SLC7A6, APLP1, CLSPN, PCAF, and PRAME) were verified by qRT-PCR. These genes functioned principally in a variety of biological processes, including oxidative stress response, DNA repair, necrosis, and cell survival. These findings indicate that Nrf2 is an important factor that performs a protective role in the suppression of oxidative stress-induced DNA damage by environmental nickel exposure. Furthermore, we describe the potential biomarkers regarded as molecular targets for Nrf2-related cellular protection against nickel exposure.
-
-
-
Proteomic Profiling of Lung Cancer Specific Plasma Proteins: Novel Diagnostic Strategy for Environmentally Exposed Male Lung Cancer Patients
By Rita SinghAbstractLung carcinomas are highly heterogeneous malignancies and the patient survival rate for lung cancer is very low. This is due to the lack of diagnostic markers for lung cancer and for predicting response or monitoring recurrence after treatments of the lung carcinomas. Human blood plasma proteomics has become one of most preferred method for cancer biomarker discovery. In this study, we used plasma for the detection of lung cancer-specific proteomic biomarker pattern by one-dimensional SDS- Polyacrylamide Gel Electrophoresis followed by nLC-MS/MS. Panels of low molecular weight proteins were found to be lung cancer specific or were not found in the parallel samples from ovarian and breast cancer plasma. To reveal the interactions of identified proteins we analyzed them by I2D - Interologous interaction software. Out of 30 identified proteins, 10 showed association with albumin. Albumin is the most abundant protein in plasma and serum and protects the smaller proteins and peptides from renal clearance. On integrating bioinformatics data with published literature 50% of identified proteins were found to be albumin associated. A list of proteins was identified such as apolipoprotein, transthyretin, haptoglobin alpha, haemoglobin, alpha-1 acid glycoprotein, zinc-alpha-2-glycoproteins known to be associated with lung cancer. To assess the potential usefulness of the identified proteomic pattern for diagnostic purpose, we raised the antibodies to the lung cancer specific proteins. Western blot analysis of lung, ovarian and breast cancer plasma samples with the lung cancer specific antibodies confirmed our findings on the specificity of the proteomic pattern to lung cancer. Validation of the lung cancer specific proteomic pattern would have significant implications for the early detection and diagnosis of lung cancer and better management of high risk patients.
-
-
-
Inactivation of the Putative Tumour Suppressor Gene DOK1 by Epigenetic Modifications in Human Cancers
By Bakary SyllaAbstractEpigenetics investigates heritable changes in gene expression that occur without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation and histone modifications, can change genome function under exogenous influence. Results obtained from animal models indicate that in utero, or early-life environmental exposures, produce effects that can be inherited transgenerationally and are accompanied by epigenetic alterations. The search for human equivalents of the epigenetic mechanisms identified in animal models is in progress. I will present evidence from human environmental studies indicating that epigenetic alterations may mediate effects caused by exposure to environmental toxicants. In these investigations, we have shown that air pollution exposure is associated with altered methylation of human repetitive elements or genes. In recent preliminary studies, we have shown alterations of histone modifications in subjects exposed to metal-rich airborne particles. I will present original data demonstrating that altered DNA methylation in blood and other tissues is associated with environmentally induced disease, such as cardiovascular disease and asthma. On the basis of current evidence, I will propose possible models for the interplay between air pollution exposure and the human epigenome.
-
-
-
Epigenetic Effects of Early Environmental Exposures on Whole Genomes and Repetitive Elements
More LessAbstractIncreasing evidence suggests that environmental exposures during in utero development impact adult health through epigenetic modifications of the genome. High production-volume chemicals such as bisphenol A (BPA), and known toxins including lead (Pb), are ubiquitous in the environment and may contribute to disease susceptibility through epigenetic mechanisms. Developmental and adult exposure to environmentally relevant levels of BPA has been shown to affect both global and gene-specific DNA methylation patterns. Preliminary studies also indicate that Pb exhibits epigenetic effects that may contribute to its known neurotoxic and obesogenic activities. During early embryogenesis, epigenetic marks, including DNA methylation, are reset at specific times in both rodents and humans. Utilizing the viable yellow agouti (Avy) mouse as a biosensor, we assess the impact of BPA and Pb on the DNA methylation status of the genome by examining coat color shifts, whole genome methylation, and repetitive element methylation. Since repetitive elements comprise nearly half of the human genome and contribute to disease when reactivated, the suppressive methylation of these elements during development is crucial to human health outcomes. Previously, only a handful of repetitive elements were known to be epigenetically variable; here we describe additional novel and environmentally responsive epigenetic elements. To illustrate the long-term biological dysregulation caused by BPA and Pb, we survey the epigenomic changes on repetitive elements and the whole genome induced by developmental exposure in mice as well as humans. The characterization of epialleles in the mouse, the most widely used model for human health, is crucial for the identification of human epialleles and the development of epigenetic therapies for the prevention and treatment of human disease throughout the life course.
-
-
-
Correlation Among Epigenetic, Environmental and Genetic Factors in Colorectal Carcinoma and Alzheimer's Disease
More LessAbstractIt has been postulated that dietary components, in conjunction with the presence of susceptibility genes, can influence the epigenome, altering genetic expression and potentially modifying colorectal cancer (CRC) as well as Alzheimer’s disease (AD) risk. The aim of two ongoing projects is to investigate the interaction of dietary components (folate levels) with genetic susceptibility (polymorphisms of genes involved in the folate metabolic pathway) in influencing the methylation levels of genes critical for colon cancer or for neurodegeneration. We are currently analyzing the methylation status of CRC related genes including RASSF1A, MGMT, APC, hMLH1, and CDKN2A in the DNA obtained from epithelial cancerous cells isolated from either early or late stage CRC tissues through immuno-magnetic method, in order to evaluate the association between methylation and clinicopathological features. Promoter methylation profiles are evaluated by means of Methylation-Sensitive High-Resolution Melting (MS-HRM) technique. Results on a subgroup of 30 CRC patients suggest that APC is the most frequently methylated gene in our cohort, and all the other genes are found to be methylated in approximately 20-25% of the cases. Several CRC patients had elevated plasma Hcy levels (above the normal range), consistent with a condition of impaired one-carbon metabolism. We also screened blood DNA from 20 late-onset AD patients, 20 healthy controls and 20 individuals with Mild Cognitive Impairment (MCI) for CpG methylation analyses in the promoter of the β-secretase gene (BACE1). Our epigenetic analysis revealed that the BACE1 gene might be subject to epigenetic regulation due to methylation/demethylation processes of different CpG islands. The outcomes of these studies comprise more knowledge of predisposing conditions (diet, genetic variants) to develop colon cancer or neurodegeneration with the possibility to undergo a primary prevention, moreover to get information on epigenetic biomarkers associated with susceptible individuals, easily detectable and useful to design a precocious diagnostic tool.
-
-
-
Serum Organochlorines Pesticides Level, Cyp1a1, Cyp1b1 Genetic Polymorphism and Risk of Breast Cancer
More LessAbstractThe aim of this study was to find the relationship between the Organochlorine and PCBs pesticides residues and female breast cancer, together with the related genetic polymorphisms, biochemical parameters and anthropometric measurements in Sudanese female breast cancer patients attending the Wad-Madina teaching hospital, Gezira State, Sudan. The prospective study was performed on 200 female breast cancer patients (of ages ranging between 25-80 years). 100 healthy persons of a range of ages and from different community areas were chosen to form a control group. The Organochlorine and PCBs pesticides residues were measured in serum and adipose tissues. We used Gas chromatographs, Thermoquest-Trace GC with 63Ni selective Electron- Capture Detector with advanced software and Nucon-GC-5765 series equipped with Nitrogen Phosphorus Detector. The genetic polymorphisms was determined the Cytochrome P- 450 (CYP1A1) in the blood and tissues. The DNA extraction by QIAamp DNA Mini Kits .PCR Technique was used for laboratory genetic analysis by using Genotypes Restriction Enzymes Length Polymorphisms (RFLP). Anthropometrics measurements were determined by weight, height and body mass index (BMI). A questionnaire was completed in order to obtain information regarding: sociodemographic characteristics, obstetric and gynaecological variables and nutritional information. The risk of breast cancer increased among women with higher serum concentrations of any Organochlorine: o, p’-DDT, p, p’-DDT, p, p’-dichlorodiphenyldichloroethylene, hexachlorobenzene, beta-hexachlorocyclohexane, trans-nonachlor, cis-nonachlor, oxychlordane, mirex, or PCBs. The high serum levels of PCBs were associated with a decreased risk of breast cancer; CYP1A1 polymorphisms were more frequent in younger patients and in patients with high level Organochlorine pesticides. Organochlorine pesticide residues may increase the risk of breast cancer in females, particularly in premenopausal women in Sudan. CYP1A1 polymorphisms probably predispose to an earlier onset of breast cancer and might be associated with a higher Organochlorine pesticides level, but further studies on a much larger group are required to substantiate our findings.
-
-
-
Cytogenetic Biomarkers, DNA Repair Efficiency and Susceptibility to Gentoxic Exposure of Lymphocytes from Persons Exposed to Low and High Doses of Iodine –131.
More LessAbstractIn case of any accidental mass exposure and particularly in cases of radiation contamination, there is a need to estimate possible effects in a short time. The best known, gold standard, accurate and associated to cancer risk increase proofed measurement of absorbed dose via classic cytogenetics is unfortunately laborious and time consuming. The aim of our human monitoring studies performed on subjects from various cities and countries was to investigate if exposures to genotoxic agents, environmental, occupational, diagnostic or therapeutic can cause a detectable increase risk. Exposures to ionizing radiation, pesticides, mercury ions, benzene related compounds have significantly elevated levels of cytogenetic damage. The 25 years follow up studies revealed significantly increased risk of cancer in the group of subjects characterized by the highest levels of the detected chromosomal damage. Results of DNA repair competence assay, with a use of challenging dose of X-rays and the detection of induced DNA damage by the SCGE assay, have correlated to levels of induced chromosome damage detected by classic and FISH cytogenetic methods. Results from studies on the influence of occupational exposure to environmental PAHs, on the efficiency of the radiation induced DNA damage’s repair, have shown a strong variability between donors and significant decrease of the DNA repair efficiency in exposed subjects, that was strongly differentiated between groups stratified first according to various genotypes for genes, encoding enzymes involved in the process of bio-transformation (CYP1A1(Ile/Val), GSTM1, NAT2) or DNA repair (EPHX4 or XRCC1)1 and then to levels of exposures. Results of our studies in various groups of (prostate or colon cancers or thyroid diseases) patients have also shown the higher levels of chromosome aberrations frequencies and associated significant reduction of cellular DNA repair efficacy in comparison to healthy subjects groups. Thyroid patients were examined first after low diagnostic 131 one, and another time five weeks after medical treatments with higher doses. Strong inter individual variability was observed. Preliminary study of polymorphisms XRCC1 and XRCC3 genes encoding enzymes involved in the repair process, confirmed strong influence of genes of the DNA damage induced by IR and stepped up levels of biomarkers, the predictor of cancer risk. Our results demonstrate also that the DNA repair competence biomarker (RCB), fast and inexpensive, can reliably detects an influence of ontogenetic or exogenous factors on biological effects, which via alteration of the DNA repair processes can rise levels of chromosome aberrations and result in increased health risk. That knowledge might be key factor in stratification of the population at risk, or in predicting beneficial range for high dose therapeutic procedures.
-
-
-
Research Strategies to Advance Our Understanding Early Life Exposures to Improve Child Health and Reduce Disease Burden.
By William SukAbstractThe environment is a fundamental determinant of human health. Targeting the best scientific research to environmental problems, wherever they arise, can lead to breakthroughs in our understanding that can be of great benefit to all. Environmental factors cause or influence an array of conditions that lead to illness and death among mothers and children, populations at greatest risk for premature death and illness. Exposures during pregnancy can influence maternal conditions during pregnancy, such as: asthma, anemia, and infectious disease susceptibility, and result in adverse pregnancy outcomes, such as: miscarriage, intra- uterine growth retardation, prematurity. These exposures can also adversely affect long-term health outcomes for the offspring, leading to chronic diseases. Developmental-stage specific exposures and windows of susceptibility are critically important since the effects of any given exposure are determined largely by the time in the developmental and maturational process when exposure occurs. Therefore, it is important to gain a better understanding of developmental toxicology: the effect of in utero exposures that may cause permanent functional changes that result in increased susceptibility to disease/dysfunction later in the life span. There is evidence that some environmental agents, especially those with endocrine agonist or antagonist activity, may alter developmental programming via alteration in gene expression or gene imprinting resulting in functional deficits that become apparent later in life. It is essential to translate research findings and knowledge into information, resources, and/or tools used by public health and medical professionals, and by the public to improve overall health and well-being. This can be accomplished by launching a globally strategic series of networks to enhance collaborations and communications between and amongst environmental health investigators, integrating investigator-initiated research, establishing and maintaining partnerships, and developing community-based primary-care and health services for vulnerable populations. The objective is fundamental: to translate the basic discoveries that prevents disease and improves health..
-
-
-
Recent Findings from the Health Effects of Arsenic Longitudinal Study in Bangladesh
More LessAbstractThe Health Effects of Arsenic Longitudinal Study (HEALS), a large multidisciplinary prospective cohort study in Araihazar, Bangladesh, was established in 2000 to evaluate the effects of a wide range of arsenic (As) exposures on various health outcomes, including premalignant and malignant skin lesions, total mortality, and children’s neuropsychological development (1). In this presentation, some important recent findings will be presented. Approximately 12,000 adults, aged 18-75, were recruited for the study; their well water As concentrations ranged from 0.1 to 864 ug/L. Since 2000, each participant has been evaluated roughly every other year. A total of 7.31, 9.95 and 2.03% of the participants completing 4 years of active follow-up reported having a chronic cough, breathing problem or blood in their sputum, respectively, as assessed by trained physicians. We found a dose-response relationship between As exposure and clinical symptoms of respiratory diseases (2). The mechanism of this effect, also reported in other countries, is not known. In particular, these adverse respiratory effects of As were clearly evident in the low to moderate dose range. We have also studied the association between As exposure and total mortality. 407 deaths were ascertained between October 2000 and February 2009. Multivariate adjusted hazard ratios for all-cause mortality in a comparison of arsenic at concentrations of 10•1–50•0 μg/L, 50•1–150•0 μg/L, and 150•1–864•0 μg/L with at least 10•0 μg/L in well water were 1•34 (95% CI 0•99–1•82), 1•09 (0•81–1•47), and 1•68 (1•26–2•23), respectively (3). Deaths due to diseases of circulatory system accounted for 43% of total mortality in the population. The mortality rate for cardiovascular disease was 214.3 per 100 000 person years in people drinking water containing <12.0 μg/L arsenic, compared with 271.1 per 100 000 person years in people drinking water with ≥12.0 μg/L arsenic. There was a dose-response relation between exposure to arsenic in well water assessed at baseline and mortality from ischaemic heart disease and other heart disease (4). The children of HEALS participants have been involved in several cross-sectional studies that examined the relationships between As exposure and several neuropsychological outcomes. We have observed dose-dependent deficits in intelligence in 8- to 11-year-old children (5, 6) and in 6-year-old children (7). More recently, we have also investigated the associations of water As and water manganese (Mn) with motor function in 304 children in Bangladesh, aged 8 to 11 years. In addition to water, we measured As and Mn concentrations in blood, urine and toenails. We assessed motor function with the Bruininks-Oseretsky Test (BOT-2), which can be summarized with a total score of overall motor proficiency (TMC) or in four subscales: fine manual control (FMC), manual co-ordination (MC), body co-ordination (BC) and strength and agility (SA). After adjustment for covariates, water As (but not Mn) levels were associated with decreases in FMC, BC and TMC; similar findings were observed when we used urinary or blood As as the exposure measure (8). Collectively, the findings from the HEALS study and a growing body of basic science and population-based evidence indicate the urgent need to provide As-free drinking water to the many affected populations around the world.
-
-
-
Impact of Air Pollution on Health of Children – Czech Experience
By Radim J SramAbstractThe Ostrava region in northern Moravia (Silesia) is the most polluted region in the Czech Republic by carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) as benzo[a]pyrene (B[a]P), especially by the steel industry. In the most polluted part of Ostrava City, Bartovice (OB), in the year 2008 was B[a]P 9.3±14.4 ng/ m3 vs control district of Prachatice (PRA) in the southern Bohemia, where B[a]P was 1.0±1.3 ng/ m3. We studied a group of 200 children living in OB (100 asthmatic and 100 healthy, aged eight-15 years) and a control group of 200 children living in PRA(100 asthmatic and 100 healthy, aged eight-15 years). As biomarkers of oxidative damage were followed 8-oxodG in urine, lipid peroxidation and protein oxidation in plasma, as biomarkers of effect gene expression profiles in lymphocytes using Illumina HumanHT-12 BeadChip and genetic polymorphisms in 768 SNPs by Illumina GoldenGate Assay. Oxidative damage by 8-oxodG was significantly higher in OB vs PRA (OR=2.27, P<0.001, 95%CI 1.40-3.70). Gene expression profiles significantly differ between OB and PRA. Comparing asthmatic vs control children, we observed nine deregulated genes in Ostrava and 17 deregulated genes in Prachatice. These changed genes are specific for each locality and asthma. Microarray results were verified by qPCR, five genes selected for Ostrava, another five for Prachatice. The verification confirmed previous results. In the asthmatic children from Ostrava were upregulated genes HPG2, AHSP and DEFA4. In the asthmatic children from Prachatice were upregulated genes SIGLEC8, CCL23, CLC and CACNG6. Gene expression profiles of asthma children seem to be specific and different in two regions. We detected also SNPs specific for the asthma children in OB. Results indicate that higher exposure to c-PAHs may induce non-allergic form of asthma bronchiale in children. We also studied the effect of exposure to B[a]P to DNA adducts, micronuclei and transcriptome in pregnancies from Prague and Ceske Budejovice. Exposure to B[a]P was three months before delivery 1.9±0.5 ng/m3 vs 3.2±0.2 ng/m3. Samples obtained from 35 mothers from Prague and 52 mothers from Ceske Budejovice were analyzed. All subjects were nonsmokers. DNA adducts were determined by 32P-postlabeling. Total DNA adducts were in cord blood 0.98±0.89 vs 1.40±1.31/108 nucleotides (p<0.001), in placentas 1.15±1.06 vs 1.94±1.80/108 nucleotides (p<0.001) from Prague and Ceske Budejovice, respectively. The frequencies of micronuclei (MN) determined by automated image analysis as MN per 1000 binucleated cells were 2.17±1.32 3.82±2.43 (p<0.001) for newborns from Prague and Ceske Budejovice, respectively. Using microarrays we assayed gene expression profiles in peripheral blood and placentas of the mothers, and in cord blood of their newborns. Comparative analysis of the profiles between the areas indicated that the pregnancies from Ceske Budejovice showed up-regulation of genes whose activity is associated with exposure to genotoxic compounds (eg, genes for xenobiotic enzymes, compensation of oxidative stress and inflammatory factors). This finding corresponded with the increased level of DNA adducts as well as micronuslei detected in the cord blood from Ceske Budejovice.
-
-
-
Establishing a Toxins in Desert Environments (TIDE) Network in Qatar
By Renee RicherAbstractObjectives: To establish a forum to discuss issues and share information related to research on Toxins in Desert Environments (TIDE network). Methods: We will solicit researchers, students, educators, and dignitaries who have published and studied desert toxins or have expressed an interest in toxins and deserts, to join a network to encourage research and an understanding of toxins in desert environments. We will target a variety of disciplines, including microbiology, zoology, botany, chemistry, anthropology, sociology, and toxicology. We will establish an interactive website to facilitate communication and hold a yearly workshop and conference in Qatar to build networking capacity and promote the network. The conference will be a three-day event including a keynote speaker and a guided field trip. Results: Topics will include information, and showcase current research and future needs for education and research on a variety of toxins as it relates to plants, animals, and people in desert environments. Human and ecosystem health will be an important focus of this group and attempts at protection and remediation will be discussed. This network will encourage and promote researchers interested in desert environments and natural and man-made toxins. Participants will liaise with other researchers and educators and foster links to maximize resources and disseminate information. Conclusions: The goal will be to cross disciplines and broaden discussions to develop a network of scientists, create international interest in the region and involve local scientists, students, and dignitaries. The desire is to establish Qatar as a center for research concerning a wide range of natural and anthropogenic toxins found in desert environments. The TIDE network will promote research, conservation and public outreach, and be a center to support scientists, students and media. The network will benefit the State of Qatar locally, but it will also draw international attention to the facilities and opportunities present, while protecting the citizens of Qatar from the potential adverse effects of toxins.
-
-
-
Genotoxic Evaluation of Occupational Exposure to Antineoplastic Agents and its Association with Polymorphisms of Enzymes Involved in DNA Repair
More LessAbstractThe increased use of combined chemotherapy in the management of different kinds of neoplasms allows us to question the adverse biological effects of occupational exposure to antineoplastic drugs, and generate studies to visualize the potential toxicity of these substances on the affected staff. Over the last few years, several reports have provided evidence about the increased presence of abortions, malformations and risk of diseases like cancer in the hospital staff responsible for the preparation and administration of these drugs. For that reason it becomes necessary to implement new methodologies to assess the genotoxic potential of these substances. Because of its sensitivity to detect mainly single chain ruptures and al-alkali labile sites in individual cells, the alkaline comet essay is an inexpensive and rapid method to evaluate the effects of these substances on the DNA of occupationally exposed staff. The aim of this study was to evaluate DNA damage in a population of individuals employed in oncology units in the city of Bogotá, Colombia and compare it with a control group. Due to genetic variants possibly determining the response to DNA damage we studied the possible effect of polymorphisms of repair genes XRCC1 and XRCC3 on damage levels of genetic material. Some characteristics and confounding factors such as age, gender, alcohol consumption, smoking, and exercise routines were also taken into account. Peripheral blood samples were obtained from 40 people between exposed workers and people from the control group. The comet essay was performed using isolated lymphocytes, for which the samples were embedded in agarose and placed on a glass slide; then they were exposed to lysis with detergent solution and finally subjected to an electric current with an alkaline buffer. The genotyping for XRCC1 and XRCC3 genes was performed by PCR-RFLP. Compared with those of the control group, partial results of exposed personnel evaluations show a significant increase in DNA damage. No influence of age, gender or time exposure was observed on the results of the comet essay. The presence of the XRCC1 polymorphism was associated with the increase of genotoxic effects of these substances, generating a greater individual susceptibility to the undesirable effect of dangerous agents. The results suggest that occupational exposure to antineoplastic drugs without the appropriate security measures can be a high risk to human health.
-
-
-
Prevention of Waterborne Disease: translating Research into Public Health Policy
By Paul HunterAbstractWaterborne disease is a major contributor to the disease burden globally, causing substantial morbidity and mortality. Whilst of most of this burden of disease falls on the very young in the poorest countries, outbreaks of waterborne disease continue to affected wealthy nations. The main influencing agency in public health policy globally is the World Health Organization (WHO). Although WHO has no statutory or legislative power with regard to water safety and the prevention of waterborne disease, the guidance documents it publishes has a major impact on national legislation throughout the world with many countries simply transposing WHO guidance directly into law. This presentation considers how scientific advice may influence WHO guidance. Initially, we will consider the nature and strength of medical and public health scientific evidence, particularly focusing on the strengths and weaknesses of expert opinion and systematic review. Systematic reviews are potentially powerful tools for summarising scientific evidence. However, as with all tools they can be misused. Furthermore, even when properly conducted, it is still not always possible to translate such reviews directly into policy. We will then consider the issue of uncertainty in the scientific evidence. Some such uncertainties can be quantified, but others cannot. The precautionary principle is often heralded as the most appropriate approach to take in such issue but this leaves the question of how unlikely a risk or costly an intervention needs to be before this is set aside. One of the key issues regarding the formulation of good policy is the influence of political lobbying. Probably the most dramatic evidence of such lobbying comes for the disclosure concerning the activities of the tobacco industry which systematically abused the scientific evidence to prevent and delay public health interventions. Perhaps a modern day example of this is the political manoeuvring over the Climate Change issue. However, lobbying is not always one- sided and other lobby groups may push for public health interventions that are not warranted. The issues will be illustrated with recourse to two case studies, one centring on Household Water Treatment and the other on the issue of the health benefits of Magnesium in drinking water. A strategic approach to incorporating scientific evidence into public health policy formulation will be set out that will include approaches such as the GRADE scheme to quantify the strength of scientific evidence and cope with uncertainty in the evidence base.
-
-
-
What Causes Seasonal Variation in Disease Prevalence and Rapid Evolutionary Changes in Virulence Mycoplasma gallisepticum?
By Andre DhondtAbstractBackground: Mycoplasma gallisepticum is a widespread bacterial pathogen that is economically important in poultry. A novel strain, causing severe conjunctivitis in wild passerines, emerged in 1994, and spread rapidly across eastern North America. In house finches the pathogen causes severe conjunctivitis. As the epidemic spread through the eastern (introduced) part of the finch’s range it caused massive declines in host abundance. In 2002 it successfully spread to the western (native) range of the host. There it spread much more slowly and disease prevalence and effects on host abundance are much lower than in the east. Mycoplasmal conjunctivitis in house finches is a system with strong seasonal variation: conjunctivitis prevalence is minimal (often zero) during the breeding season (April July); In late summer and fall, prevalence increases gradually reaching a maximum in October to November. In December, prevalence reaches a new low, followed by a second smaller peak in late February and early March, after which prevalence returns to the breeding season minimum. The objective was to 1. determine the factors driving seasonal variation in disease prevalence, and test the hypothesis that relapse of recovered individuals can be the origin of fall epidemics; and 2. determine factors driving changes in virulence once the disease is established. In the first study, birds not previously exposed to Mycoplasma gallisepticum were held in large aviaries. After one individual had been inoculated and horizontal transmission had caused all birds in the group to be exposed, birds recovered and were allowed to breed. In September naïve juveniles were added to the group and to test if the recovered adults would infect them. In March, when disease prevalence was declining naturally, Mycoplasma gallisepticum was reintroduced in the flock. In the second study, birds were sequentially exposed with two Mycoplasma gallisepticum strains that differed in virulence to test for cross‐immunity between strains. The first result showed n naive juveniles added to a flock of asymptomatic, fully recovered adults became infected with Mycoplasma gallisepticum showing that previously‐exposed, recovered and asymptomatic individuals can be the source of a new epidemic. The introduction of Mycoplasma gallisepticum in March, when in the wild disease prevalence is low to zero, caused a new outbreak whereby previously exposed and recovered individuals relapsed. The second result showed that after recovery individuals reinfected with a more virulent strain became very sick, while individuals reinfected with a less virulent strain were resistant to reinfection. We drew two conclusions from the study. First, that asymptomatic individuals can be the source of a new outbreak. The introduction of the pathogen in recovered groups is sufficient to cause a new disease outbreak. Seasonality in outbreaks is most likely tightly linked to seasonal variation in bird movements and behavior, rather than with external seasonal drivers. Secondly, in this system there exists partial cross‐immunity, whereby more virulent strains are able to cause disease in individuals recovered from a previous infection with a less virulent one. This result has two implications. First partial cross‐immunity selects for more virulent strains in nature. Second, incomplete vaccination would also cause an increase in pathogen virulence, which might have implications for vaccination strategies in humans.
-
-
-
Effect of TiO2 Nanoparticles in Human Cells from Healthy Individuals and Patients with Respiratory Diseases
More LessAbstractNanotechnology has preceded nanotoxicology and little is known of the effects of nanoparticles in human systems, let alone in diseased individuals. Therefore, the effects of titanium dioxide (TiO2) nanoparticles in peripheral blood lymphocytes from patients with respiratory diseases (lung cancer, chronic obstructive pulmonary disease (COPD) and asthma) were compared with those in healthy Individuals to determine differences in sensitivity to insult from nanoparticles. Ethical permission was obtained to collect peripheral blood lymphocytes from respiratory disease patients and healthy individuals. The Comet assay was performed according to guidelines recommended by Tice et al (1). The micronucleus assay was conducted according to Fenech (2) and ras oncoprotein detection according to Anderson et al (3). The means of Olive tail moments and % tail DNA in peripheral blood lymphocytes were compared in the Comet assay after treatment for 30 minutes with different non-cytotoxic TiO2 concentrations (10, 30 and 50 µg/ml), as well as the negative control of untreated lymphocytes and the positive control of 80 µM (2.72 µg/ml) H2O2 . The results showed statistically significant concentration–dependent DNA damaging effects of TiO2 in both respiratory patient and healthy control groups. In the micronucleus (CBMN) assay, micronuclei (MN) per 1000 binucleated cells of healthy controls, lung cancer, COPD and asthma patients were examined after treatment of blood cultures with two different TiO2 concentrations (5 and 10µg/ml), as well as the negative control of untreated blood cultures and the positive control of 0.4 µM MMC. There was an increase in micronuclei without statistical significance when compared with the untreated control of the patients, but with significance when compared with the negative control of healthy individuals. Furthermore, when modulation of ras p21 expression was investigated, regardless of TiO2 treatment, only lung cancer and COPD patients expressed measurable ras p21 levels.
-
-
-
Environmental Determinants of Malaria Transmission in Africa
More LessAbstractA new mechanistic and spatially-explicit model of hydrological and entomological processes that lead to malaria transmission has been developed recently at MIT. This unique model was tested against field observations from Africa. HYDREMATS (Hydrology, Entomology, and Malaria Transmission Simulator) is described in (Bomblies, Duchemin, and Eltahir, WRR, 44, 2008). HYDREMATS is suitable for low cost screening of environmental management interventions, and for studying the impact of climate change on malaria transmission. Examples of specific applications will be presented for two villages from Niger in Africa.
-
-
-
Insects as model animals to examine the harmful effects of agricultural pesticides on the environment
More LessAbstractChanges in modern agricultural practice have allowed an increased production of fertilizers, herbicides and other pesticides causing important negative effects on the environment worldwide. Organic fertilizers are also extensively applied to agricultural lands, but they can contain bacteria and a large variety of microbial communities and parasites that can be rather pathogenic for wildlife. Also, because trace elements are often added to poultry diets to increase resistance to diseases of farm animals, poultry litter can also contain trace elements which are potentially toxic to living systems when present in high concentrations. We have examined experimentally the effect of commonly used mixtures of organic and mineral fertilizers and herbicides on the mortality of insects. Mealworms of Tenebrio molitor (n = 300) were exposed for four weeks to four different treatments: organic liquid fertilizer (pig manure), organic solid fertilizer (turkey litter), mineral fertilizer (nitrates), and herbicides (a mixture of glyphosate and 2, 4-D). After four weeks in direct contact with all treatments, mealworm mortality ranged from 74 percent to 88 percent. Surprisingly, control mealworms placed in the same room with the other treatments also experienced high mortality (72 percent) while mortality of control-isolated mealworms was low (eight percent), suggesting that volatile compounds from tested products can be noxious to insects. Our results also indicate that more individuals escaped from the herbicides and nitrate treatments than from the others, suggesting some kind of behavioural avoidance of toxic environments. The traditional organic fertilizers appear to be less toxic than inorganic fertilizers for the species studied. Organic fertilizers from farms should be adequately treated before being dispersed into the environment. Also, mineral fertilizers and herbicides should be used with moderation and well in the prescribed proportions to reduce their damage to the environment.
-
-
-
The Relevance of the Deer as an Animal Model for Studying the Contaminant Effect on Early Embryo Development
More LessAbstractNowadays, environmental contaminants are a ubiquitous part of the ecological scenario, as is the ability of many of these chemicals to alter embryo development. There is therefore a need for researching and clarifying the effects of contaminants during different phases of early embryo development in humans. The use of alternative animal models may provide new insights into research on human embryo development, and the Iberian red deer may be a viable option. The main advantage of this animal model is the availability of samples which have not been sacrificed for this purpose, as we have access to samples (mature spermatozoa and oocytes) from animals killed during hunting activities. Therefore, our aim was to optimize the system that allows us to carry out in vitro fertilization (IVF) in deer, to then assess the effect of different contaminants on embryonic development. The aim of this work was to test two different oxygen concentrations (5 percent or 20 percent) on the in vitro fertilization. We have also assessed the addition, or not, of fetal calf serum (FCS) during embryo culture after IVF. Ovaries and testicles were transported to the laboratory at 20 ºC. Oocytes were matured in TCM 199 supplemented with 10 percent foetal calf serum, 100 mM cysteamine and 10 µgmL-1 FSH and LH during 24 h with 20 percent CO2. Matured oocytes were inseminated with thawed epididymal spermatozoa during 18 h at 38.5ºC with 5 percent or 20 percent O2.The presumptive embryos were cultured with synthetic oviductal fluid (SOF) supplemented with FCS at 0 hour, at 2 days post insemination (d.p.i.), 4 d.p.i. and without FCS at 38.5ºC with 5 percent CO2. Our results showed that treatment rendering best results for cleavage and blastocyst rates included five percent oxygen and embryo culture without fetal calf serum, as these conditions are quite similar to those used in human IVF. In conclusion, the optimization of the in vitro embryo development system in deer might prove useful information for the role of contaminants during this critical physiological period. Alternative animal models may contribute to advance our understanding of the effect of contaminants on early embryo development in humans.
-
-
-
Maintaining Drug Quality Standards
More LessAbstractMedicines are manufactured, sold, distributed, and dispensed across the globe today, bringing enormous benefits for patients. However, this globalisation has also increased the spread and prevalence of medicines that are unsafe or may be ineffective. Substandard medicines, according to the WHO, are “products whose composition and ingredients do not meet the correct scientific specifications and which are consequently ineffective and often dangerous to the patient”. Substandard drugs are able to gain approval in countries that do not have robust regulatory standards for drug quality. Legitimate generic medicines meet accepted regulatory standards, typically through bioequivalence evaluation with rigorous identity and quality testing verified by a stringent regulatory evaluation process. These quality drugs provide a vital and cost-effective way to meet the pharmaceutical needs of patients around the world. Substandard medicines can arise due to the lack of scientific expertise of the manufacturer, problems with the manufacturing processes and/or quality and testing system deficiencies. The negative consequences of substandard drugs are serious and can contribute to significant mortality and morbidity due to treatment failure, toxicity or promotion of drug resistance. The theoretical scientific concerns regarding comparability between different versions of drugs containing the same active ingredient (originator, generic or substandard) have been borne out in investigations of the purity and clinical performance of specific copies relative to the originator drug. These studies can reveal insight into the extent to which substandard drugs have become available around the world and the impact they can have on healthcare. This presentation will present an overview of the healthcare issues that arise due to substandard drugs. The presentation will give examples of clinical and technical issues that give rise to substandard drugs and the potential impact of these formulations on individual patients and healthcare systems.
-
-
-
Health Impact of Substandard Medicines in the Developing World: Risk of Genotoxic Impurities
More LessAbstractSubstandard medicines are becoming a global concern that is particularly endemic in developing countries. According to the WHO Substandard medicines are genuine drugs produced by legitimate manufacturers which do not meet the recognized quality and purity standards. A substandard drug is a medicine that does not meet specifications necessary to ensure quality, efficacy and safety; has not demonstrated bioequivalence to the originator; or does not have sufficient evidence to demonstrate originator data can be referenced. In general the substandard drugs are copies of medicines that have been approved in countries with limited regulatory standards and thus might not be made to high quality standards or be sufficiently tested to be approved in countries with more stringent regulatory standards and controls, eg, US, EU, Japan, and Australia. The synthesis of pharmaceutical products frequently involves the use of reactive reagents and the formation of intermediates and by-products. Low levels of some of these may be present in the final drug substance and/or drug product as impurities resulting either from the synthesis process or from degradation. Such chemically reactive impurities may have the potential for unwanted toxicities including genotoxicity and carcinogenicity. So, besides not providing any benefit to patients they may, if not tightly controlled, be hazardous. The pharmaceutical industry and the regulatory agencies (e.g. US-FDA, EMA) recognize their respective obligation to limit specifically genotoxic impurities. Therefore, substantial efforts are made during development to control all impurities at safe concentrations. Control of impurities in the drug substance and degradants in drug product are addressed in the respective ICH Quality Guidelines. Justification of limits per these ICH guidelines is normally based on the qualification of batches of the active pharmaceutical ingredient including its impurities in pivotal toxicity studies that include genetic toxicology tests. According to current regulatory practice it is assumed that genotoxic compounds with a direct interaction with DNA have the potential to damage DNA at any level of exposure and that such damage may lead/contribute to tumor development. Therefore the use of poor quality and potentially harmful substandard medicines especially with high levels of genotoxic impurities could lead to therapeutic failure, exacerbation of disease, resistance to medicines and sometimes death.
-
-
-
Genomic Alterations in Non-Cancer Diseases
More LessAbstractIn spite of their multitude and obvious clinical diversities, cancer and other chronic degenerative diseases may share common risk factors and protective factors as well as common pathogenetic determinants, such as DNA damage and repair, epigenetic events, oxidative stress, and chronic inflammation. We applied the same biomarkers that are usually exploited in cancer research to investigate genomic and post-genomic alterations occurring during critical periods of life, such as pregnancy, the perinatal period, and aging. Molecular and cellular alterations were detected in cancers associated with chronic viral infections, physical agents, individual chemicals or complex mixtures, as well as in other chronic diseases, including atherosclerosis, degenerative heart diseases, chronic obstructive pulmonary disease, skin alopecia, ocular diseases, and neurodegenerative disorders. Not only DNA damage and repair but also alterations of the microtubule-associated protein tau, which are involved in Alzheimer’s disease, were detected in cigarette smoke-related neurodegeneration. The proliferation rate is the main factor that affects the possible evolution towards a given disease. In fact, the aforementioned pathogenetic mechanisms may evolve (a) into cancer when they occur in highly proliferating cells, (b) into atherosclerotic plaques when they occur in the smooth muscle cells of the artery medium layer, and (c) into genuinely degenerative diseases when they occur in perennial, postmitotic cells, such as cardiac myocytes and neurons, being thus associated with cardiomyopathies and neurodegenerative diseases, respectively.
-
-
-
Environmental Mutagenesis In Cardiovascular and Eye Diseases
More LessAbstractTo check the pathogenic role of exposure to mutagens in cardiovascular and eye disease we examined molecular damages in affected subjects. 107 atherosclerotic patients were tested for molecular alterations in aorta specimens and molecular biomarkers evaluated for their prognostic value in a 15-year follow up. Mitochondrial damage (mitochondrial DNA common deletion 4977 bp) and oxidative DNA damage (8-oxo-dG), detected at very high level in atherosclerotic aorta, were significantly related with patients survival. Physical activity dramatically decreased these biomarkers, improving survival, although with a remarkable inter-individual variability. Indeed, preventive effects of physical activity were mainly detected in patients bearing double GSTM/T homozygous deletion, which have a 3.6-year survival only in case of being sedentary while a 9.7-year survival in case of being physically active (a 30-minute walk a day). Dealing with ocular diseases, we analyzed 73 patients affected by glaucoma, the most common cause of irreversible blindness worldwide, as compared to 158 unaffected controls for the occurrence of molecular damage in the ocular trabecular meshwork, the tissue regulating aqueous humor outflow. Oxidative nuclear DNA (8-oxo-dG) and mitochondrial DNA damage (mitochondrial DNA common deletion 4977 bp) were consistently detected and tightly related with clinical variables, including intraocular pressure increase and visual field defects. Mitochondrial damage in trabecular meshwork results in apoptosis activation and cell loss, as demonstrated by proteome analysis of aqueous humor. On a comparative basis with iris and cornea, trabecular meshwork resulted to be the most sensitive tissue of the ocular anterior chamber to oxidative damage when ocular tissues collected from corneal donors were challenged with hydrogen peroxide. In the same experimental system we demonstrated that beta blockers and carbonic anhydrase inhibitor drugs, commonly used in glaucoma therapy, are able to attenuate DNA and mitochondrial damage as induced by reactive oxygen species in trabecular meshwork. These studies provide experimental evidence that molecular damage as induced by exogenous and endogenous mutagens play a pathogenic role in cardiovascular and ocular diseases by inducing nuclear and mitochondrial DNA damage.
-
-
-
Association Between the Environmental Risk Factors and Chinese Male Semen Quality
By Jia CaoAbstractIn order to analyze the trend of change in semen quality of Chinese healthy men over recent 25 years, a total of 115 reports were collected on quality inspection of semen of healthy Chinese men between 1985-2009 through literature search. This involved 23,126 people from 69 counties and cities in China. The results indicated that the semen concentration of healthy Chinese men appears in possible decline over the last 25 years (P < 0.05). A cross-sectional study in our group was performed to evaluate the semen quality of 1346 healthy men residing in Chongqing area of south-west China in 2007. We analyzed urinary levels of PAHs and PAEs metabolites and assessed semen quality, sperm DNA damage, and sperm apoptosis in 232 men from the population. The data indicates that the environmental level of PAH exposure is associated with increased sperm DNA damage, but not in the semen quality. These findings suggest that exposure to PAHs may disrupt the genetic integrity of sperm and thereby interfere with Chinese male fertility. Meanwhile, we observed weak associations between MBP of PAE metabolites and sperm concentration in Chongqing general population. This suggested that the Chinese general population exposure to the environmental level of PAEs may cause a reduction in sperm concentration. We observed no significant association between other phthalates and reproductive biomarkers suggested that phthalates may vary in their reproductive toxicity.
-
-
-
Induction of Germ-cell Mutations by Particulate Air Pollutants
By Carole YaukAbstractThe particulate component of urban air pollution contains many compounds that are genotoxic and carcinogenic. Anthropogenic particulates are primarily derived from vehicle and power plant emissions, and various industrial sources. Particulates contain polycyclic aromatic compounds and metals that are known to be either directly or indirectly mutagenic through the creation of DNA adducts and oxidative stress. Although the regulation of acceptable levels of exposure to air pollution are primarily based on cardiopulmonary effects, data from our lab suggest that germ cells are a highly sensitive cell type that are responsive to low levels of particulate air pollution exposure. DNA damage in germ cells can lead to heritable mutations that may result in a wide variety of detrimental outcomes, from embryonic lethality to genetic disease in the offspring. Thus, hazards to germ cells are critically important to evaluate in the context of the health of future generations. Work in our laboratory examines the genetic and epigenetic consequences of parental exposure to particulate air pollutants on their gametes and their unexposed descendants. Our work applies highly unstable repetitive elements in the genome to measure induced mutation in pedigrees or sperm samples of mice. These studies have demonstrated that exposure to various sources of particulate air pollutants cause DNA mutations at repetitive sites in the germline that are inherited. Exposure of male mice to air pollutants leads to increased DNA strand breaks, DNA mutations and altered DNA methylation in sperm. Exposure of male in utero to diesel exhaust particles causes an increase in inherited mutation in their unexposed descendants. Mice exposed to both mainstream and sidestream tobacco smoke at environmentally relevant levels show similar increases in mutation frequency, above those doses leading to induction of somatic mutation. The data demonstrate that particles derived from combustion cause mutation in gametes, possibly mediated by epigenetic events. The mechanisms linking particle exposure and inherited mutation remain elusive but are the subject of research in our laboratory.
-
-
-
Privacy and Ethics in Human Biomarker Studies
More LessAbstractHuman biomarker studies support the understanding and prevention of environmentally induced adverse health effects. However, using human samples and data related to human health raises sensitive issues related to ethics and privacy and is subject to various regulations/rules. Overall emphasis is primarily on decisional autonomy and protection of individual rights. The collective need to protect health as a public asset is less valued. The question is whether study subjects are adequately and equally protected in current practices and whether progress in environmental health research is still safeguarded. Scientific needs have to be balanced with rights of study subjects. At the same time samples and data should be used at maximum to the benefit of all, which might include secondary uses of samples/data. Decision making processes should take into account respect for human dignity and equality of moral status of all individuals, social justice, solidarity and democratic participation as appealing values and useful complements to the four conventional bioethical principles. Trust and confidence are needed to promote voluntary participation in studies. An adequate communication at all stages of the study is of key importance.
-
-
-
Establishment of Ethical Research Committees in Developing Countries
By Wagida AnwarAbstractThe majority of biomedical research has been predominantly motivated by concern for the benefit of the communities. Therefore, establishment of Research Ethics committees is essential for communicating bioethical issues and ethical perspectives when we are carrying out Genetic Toxicology research. These committees need to follow the international standards and to set up guidelines to follow to evaluate the research projects. International guidelines can assist in strengthening the capacity for the ethical review of biomedical research in all countries contributes. The ethical and scientific standards for carrying out biomedical research on human subjects have been developed and established in international guidelines, including the Declaration of Helsinki, the CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects, and the WHO and ICH Guidelines for Good Clinical Practice. Compliance with these guidelines helps to ensure that the dignity, rights, safety, and wellbeing of research participants are promoted and that the results of the investigations are credible. Ethical and scientific review of biomedical research is required alongside informed consent as essential measures to protect the individual person and the communities who participate in research. Biomedical research includes genetic toxicology research, research on pharmaceuticals, medical devices, medical radiation and imaging, surgical procedures, medical records, and biological samples, as well as epidemiological, social, and psychological investigations. As an example, in Egypt, the Ministry of Higher Education created The Egyptian National Bioethics Committee (NBC) in 1996. The mission of the committee is to serve as the international contact organization for bioethics, especially with regard to the communication with the UNESCO. It gives advice to and cooperates with the other Egyptian committees that deal with bioethical issues and raise awareness for bioethical questions in Egypt. The committee has established working groups, for medical and pharmaceutical applications, for food and agricultural applications, and for information. It sees itself as counterpart of the International Bioethics Committee (IBC) of the UNESCO. The NBC has issued reports on conducting biological and medical research, on human organ transplantation, surrogate motherhood, and scientific research on gene therapy. The NBC has members with different education, e.g. medicine, agriculture, biology, law, religious and social sciences. Since the 1980s Egypt has hosted a number of regional and international conferences, dealing with bioethical questions. Furthermore, several Egyptian universities and research centers established ethical committee and they are very active in improving the quality of their performance through networking and training programs.
-
-
-
Ethical Guidelines for the Use of Biological Samples in Human Research
By Eman SadounAbstractHuman biological materials have been, and continue to be, invaluable resources for a wide variety of research activities. Researchers and clinical investigators relay on the availability of stored human biological materials as well as the willingness of individuals to participate in research protocols by donating blood, tissue, or DNA samples to research. This ongoing process raises a number of ethical issues. This necessitates a distinct policy to facilitate proper management of these activities. The Research Department at Supreme Council of Health (SCH) has developed a policy on the use of stored data and biological samples in human research. Dr Eman Sadoun will present the SCH policy guidelines. The guidelines provided in the policy are intended to promote the goals of improving health through biomedical and environmental research while protecting the rights and welfare of those individuals who contribute to human knowledge through the donation of their biological materials. Such guidelines, while seeking to protect patient confidentiality and autonomy, are also developed to ensure that appropriate access for legitimate research purposes is maintained.
-
-
-
Grey Areas, Controversies and Possibilities in Ethical Review of Environmental Health Research
By Kip KanteloAbstractThis presentation will provide an overview of considerations facing research ethics boards and human research protection programs in the handling of environmental health research. Based on the ethical principles and regulatory requirements underlying the Qatari and American human research protections systems, the presentation will briefly examine issues such as:
- - determining what constitutes "human subjects research".
- - providing the appropriate level of review.
- - evaluating risks and benefits.
- - showing due respect to subjects.
-
-
-
Environmental Impact Assessment: What, When, How?
More LessAbstractEnvironmental Impact assessment (EIA) is a term that has become widely known in both developed and developing countries. It is well-recognized that EIA talks about the process by which the environmental impacts of a project can be systematically collected, analyzed and well- presented to inform and assure a proper decision making process [1]. The measures would include air quality, water quality, soil contamination, restoration, noise pollution, and others. The activities undertaken during decision taking stages to monitor, evaluate, manage and communicate the environmental outcomes, were EIA methods, tools and techniques ranging from simple to complex, requiring different kinds of data, different data formats, and different levels of expertise for their interpretation [2]. The EIA practitioner is faced with a vast quantity of raw, and usually disorganized, information that must be collected and analyzed in preparation for an EIA report. This EIA report that accompanies the Planning Application is usually called the Environmental Impact Statement (EIS), This report shows that the significant effects of a development, both positive and negative are objectively analyzed. Upon receiving this information it is determined whether the development should go ahead or not; it also helps to predict the effects and scope for reduction [3]. EIA is not only a tool for decision makers, it is also a tool for the designers and developers to ensure that they best minimize local adverse impacts and derive maximum benefits from a development with environmental enhancement [4]. This project will review the environmental Impact Assessment process, indicating how this fits in to the planning process but equally how it can be used as design guide for a factory planning and construction. The study project will address the following questions: What is an Environmental Impact Statement (EIS)? When is it required? What is the process of an Environmental Impact Assessment (EIA)? What are the environmental, social and economic issues associated with construction developments? How do you assess them and mitigate for them? Are there any local policies and laws under town planning regulations that regulate the EIA? How does the regulatory body decide whether to grant permission? How does the regulatory body enforce any mitigation requirements following construction?.
Sponsored by the National Institutes of Health.
-
-
-
DNA Ligases I and III Cooperate to Mediate Alternative Non-homologous End-joining in Vertebrates
More LessAbstractIn eukaryotes, the three families of ATP-dependent DNA ligases are associated with specific functions in DNA metabolism. DNA ligase I (LigI) catalyzes Okazaki-fragment ligation at the replication fork and nucleotide excision repair (NER). DNA ligase IV (LigIV) mediates repair of DNA double strand breaks (DSB) via non-homologous end-joining (NHEJ). The evolutionary younger DNA ligase III (LigIII) is restricted to higher eukaryotes and has been associated with base excision (BER) and single strand break repair (SSBR). We show that in vertebrate DT40 cells, in the absence of LigI, LigIII efficiently supports semi-conservative DNA replication via an alternative DNA replication pathway, as well as NER. LigIII also supports an alternative, low efficiency, NHEJ process that operates as backup to LigIV-dependent NHEJ. Together with its exclusive and essential function in mitochondria, these observations elevate LigIII to a universal ligase, equipped to substitute or backup the functions of all other DNA ligases.
-
-
-
DNA Damage Response in UV Irradiated Cells
More LessAbstractNucleotide excision repair (NER) removes bulky DNA lesions from the genome. The toxic effects of these lesions relate to their potency to block replication and transcription elongation. Two mechanistically distinct NER subpathways have been identified: Global genome NER (GG-NER) and transcription-coupled repair (TC-NER). In the currently prevailing model, NER factors are sequentially assembled into pre- and post-incision complexes; however, the regulation of NER in vivo is poorly understood. I will focus on GG-NER particularly on damage recognition and mechanisms that control the transition from dual incision to repair synthesis and UV induced signalling. Moreover, we provide evidence that damage signalling in nondividing cells proceeds via NER dependent and independent UV photolesion processing. The second part of my talk deals with TC-NER in UV-irradiated cells. Deficiency in TC-NER is a hallmark of the rare human disorder Cockayne syndrome (CS). Two complementation groups (A and B) have been identified. Both CS proteins have distinct functions in recruitment of NER factors and chromatin remodelers. The emerging picture of TCR is complex: repair of transcription blocking lesions requires the NER factors, chromatin remodelers and at least two essential assembly factors, ie the CSA and B proteins. Together these, and yet unidentified proteins, will accomplish not only efficient repair thereby counteracting mutagenesis and cytoxicity but also contribute to DNA damage signalling events.
-
-
-
DNA Damage and Apoptotic Signaling Following Sunlight
More LessAbstractSunlight induces DNA damage due to the ultraviolet (UV) components UVA and UVB. Pyrimidine dimers (CPDs and 6-4PPs) are the most toxic lesions induced by sunlight, and are mainly induced by UVB light, although these lesions are also potentially induced by UVA. On the other hand, UVA light is known to indirectly generate oxidative species, which also damage DNA. By using DNA repair deficient cell lines from xeroderma pigmentosum (XP) patients, expressing pyrimidine-dimer-specific photolyases, we investigated the biological relevance of these lesions in cell killing induction after UVA-irradiation. The results clearly indicate that both CPDs and 6-4PPs are important lesions inducing cell killing, including apoptosis, although other lesions also participate in the events that lead to cell death by UVA. XP cell lines were also employed as sensitive cell targets for the development of sunlight cell dosimeter, which can be useful to analyze the ability of sunscreen filters to protect them from irradiation. Again, although sunscreen filters provided some cell protection from the ability to induce pyrimidine dimers, other types of DNA damage (probably mainly related to UVA) also efficiently induce cell death, reducing the protection factor of normally employed sunscreen filters. Thus, DNA lesions probably induced by oxidative reactive species are also biologically relevant when considering sunlight effects in human cells, and these lesions are also important when considering the sensitivity of XP patients.
-
-
-
Mechanisms of Transcriptional Inhibition and Induction by Environmental Mutagens
More LessAbstractExposure of cells to environmental mutagens activates cellular responses, leading to a reprogramming of gene expression by mechanisms that are not fully elucidated. To investigate the mechanisms of how environmental mutagens affect global gene expression in human cells both at the level of RNA synthesis and transcript stability, we developed a new technique, called BruChase-Seq, based on bromouridine (BrU) pulse-chase labeling coupled to deep sequencing. Using BruChase-Seq we found that ionizing radiation, cadmium or the pro-inflammatory cytokine TNF rapidly altered both the synthesis and the transcript stability of specific sets of genes in human fibroblasts. To directly assess the effect of UV light on nascent RNA transcription, we developed BrUV-Seq, where cells are irradiated with UV-light immediately before labeling nascent RNA with BrU. We found that UV-induced DNA lesions inhibited transcription elongation but not initiation, leading to a dramatic enhancement of sequencing signal at transcription start sites. Unexpectedly, we found that UV-irradiation also caused an enrichment of non-coding RNA and enhancer sequences, potentially making it possible to use BrUV-Seq to map poorly annotated non-coding RNAs and active enhancer elements genome-wide. We believe that the BruChase-Seq and BrUV-Seq approaches will be useful in elucidating the mechanisms of gene regulation in many biological settings.
-
-
-
DNA Repair and Damage Response Following Exposure of Cells to Alkylating Carcinogens
By Bernd KainaAbstractAlkylating carcinogens are widely distributed in the environment and are present in food, beverages and tobacco. They are also endogenously formed in stomach and gut. These agents induce a dozen different DNA lesions, and some of them have been identified to be carcinogenic, clastogenic, recombinogenic and cytotoxic. A critical DNA adduct is O6-methylguanine (O6MeG). This damage causes mutations and is responsible for most of the carcinogenic effects of simple alkylating agents. At the same time, O6MeG is a highly powerful cytotoxic lesion, giving rise to the induction of apoptosis, necrosis and autophagy. The damage is repaired by the suicide enzyme alkyltransferase (MGMT), which is a very important first-line defense mechanism and biomarker of alkylating drug resistance, both in normal tissue and tumors (therefore it also plays a key role in tumor therapy). MGMT knockout mice respond to alkylating agent treatment with a high yield of colon cancer. The same is true for MPG ko mice defective in base excision repair, indicating that not only O6MeG, but also non-repaired N-alkylation lesions give rise to mutations and cancer. Elimination of pre-transformed cells by apoptosis counteracts this process. We have shown that O6MeG is a very powerful trigger of apoptosis, which is executed via the death receptor and the mitochondrial damage pathway. The apoptotic response is downstream, triggered by DNA double-strand breaks (DSB) that are formed during the mismatch repair dependent processing of O6MeG. These O6MeG-induced DSBs are repaired by homologous recombination (HR), which is a second-line defense against O6MeG triggered cell death. Other players involved in DSB recognition and HR are NBS-1, ATM, Rad51, XRCC2 and XRCC3. In some cell types, the efficiency of O6MeG to trigger the p53 dependent death receptor pathway is higher than the p53 independent endogenous mitochondrial pathway, which rests on p53 driven death receptor upregulation. However, p53 is also able to upregulate DNA repair genes thus protecting against mutations and cell death. The implications for human defense against environmental carcinogens will be discussed. Work was supported by DFG KA724.
-
-
-
The Possible Cancer Chemopreventive Activity of Spice Ginger
More LessAbstractGinger extract and its active principles, gingerol and shogaol, were tested in a different model system for their antimutagenicity activity. Salmonella/microsome is a short-term assay developed to detect human carcinogens as mutagens were used for these studies. Ginger extract, gingerol and shogaol in a two model system, inhibited the formation of mutagenic glucose + lysine in TA100 without metabolic activation (S9mix) and glucose + lysine + creatinine pyrolysates in TA98 with S9mix. The observed inhibition of mutagenicity by gingerol and shogaol is by direct interaction. Ginger extract, gingerol and shogaol also inhibited the formation of mutagenic nitroso-compounds from dried fish extract and nitrite at pH2.0. Ginger extract, gingerol and shogaol dose dependently inhibited aflatoxin and benzo(a) pyrene (BP)-induced mutagenicity in TA98 with S9mix. Ginger extract, gingerol and shogaol lowered the excretion of urinary mutagens in BP fed mice. In the same animal there was a decrease in DNA damage as determined by decrease in the bone marrow micronuclei. Finally, feeding 0.5g of ginger decreased urinary excretion of mutagens in active and passive cigarette smokers. These results suggest that ginger in the human diet may act as a novel cancer chemopreventive agent through diverse mechanisms.
Moolky A*., Kolpe U.,** Satish B.S*., Nagabhushan M., Loyola University Chicago, Illinois, USA** University of Illinois at chicago, Chicago, Illinois, USA & Manipal University, Manipal, India*
-
-
-
An Assessment of Chromosomal Damage in Individuals Occupationally Exposed to Domestic Cooking Gas
More LessAbstractThe lymphocytes of healthy adult men occupationally exposed to Domestic Cooking Gas (DCG) were screened for genotoxic damage using the Cytochalasin Block Micronucleus [cytome] (CBMN) Assay. Results obtained, show that there was a significant increase in the the induction of binucleated micronuclei frequency (BNMN) in subjects exposed to DCG as compared with the non-exposed controls, with a 92 percent increase in the degree of induction. There was a positive correlation between the degree of micronuclei induced and the duration of exposure (r2 = 0.78). A higher proliferation rate (1.58 ± 0.3), as calculated using the Nuclear Division Index (NDI) was found in the exposed group as compared with the control group (1.36 ± 0.05).
The observations above suggests that DCG may induce chromosomal damage and cell proliferation in vivo.
-
-
-
The Impact Of Bacteriophages In Bacteria Removal Associated with Soba Stabilisation Station Efficiency
More LessAbstractBacteriophages are viruses that infect and lyse bacteria, the applications of phage techniques in wastewater treatment systems improve effluent and sludge emissions into the environment. The existence of bacteriophages in wastewater of the Soba Stabilisation Station was determined by isolating and identifying methods for their activities against Escherichia coli and Staphylococcus aureus isolated from the anaerobic, facultative and maturation ponds. The general viable count of the bacteria showed an average of 2.0 x 106 cfu/ml. In broth media the affection of the bacteriophage interactions with bacteria showed an increase of bacteriophages with concomitant decrease in bacteria due to culture clearance, where the readings of the turbidity for the first and second infection showed statistical significant light transmission among E. coli phage samples due to placing of sample collections as follows: from the anaerobic and facultative ponds P>0.05, facultative and maturation P<0.05 and anaerobic and maturation P>0.05., whilst the S. aureus phage samples’ light transmission from the anaerobic and facultative P<0.05, facultative and maturation P<0.05 and anaerobic and maturation P>0.05. On solid media, the affection of the bacteriophage was recognised by the phage plaque formation on bacterial cultures. The linear equations of phage densities and distributions according to their wavelength were y = 0.0008x + 0.0303 for E. coli phage and y = -0.0102x + 0.2438 for S. aureus phage.
This study concluded that phages are naturally present, where their hosts are present, and naturally destroyed bacteria which aided recovery from a polluted environment.
Keywords: Bacteriophage/ Escherichia coli/ General viable count / Light transmission/ Linear equations/ Stabilisation Station /Staphylococcus aureus/.
-
-
-
Risk Assessment of Local Belacan (Shrimp Paste) Intake
More LessAbstractShrimp paste is one of the staple food condiments in Malaysia. This research was conducted to evaluate the mutagenic activity of local shrimp paste, and to estimate the actual intake among the Malaysian population. Two types of shrimp paste, produced from a factory and small scale industry (SSI), were sampled from Melaka, Malaysia and extracted with aqueous and methanol solvent. Ames Test was used to determine the mutagenicity potential of shrimp paste using Salmonella thyphimurium TA98 and TA100 bacterial strains.
There were mutagenic activities in methanol extracts of shrimp paste from SSI at 25 mg/ml and 50 mg/ml without the presence of metabolic activator S9 in TA98 strain. In the presence of metabolic activation, the same extract showed mutagenicity response at 50 mg/ml in TA 98 strain. a Semi Quantitative Food Frequency Questionnaire (FFQ) was used to evaluate the actual intake of shrimp paste among the population using multistage random sampling. The mean daily intake of shrimp paste was 1.41±0.27 g/day. Heavy metal analyses were also determined by ICP-MS. Arsenic (As) and Lead (Pb) were found to exceed the limit of Malaysian Food Act 1983 and Food Regulation 1985 (As from factory = 8.69±1.67 mg/kg, As from SSI = 12.14±2.32 mg/kg, Pb from SSI = 10.23±1.12 mg/kg).
From this study, it has been observed that the daily intakes of As, Pb, Cd and Hg in shrimp paste is much lower than the provisional tolerable weekly intakes (PTWI) given by FAO/WHO and could not be considered harmful to the population. The outcome of this research can be used as baseline data for the safe intake of shrimp paste as a daily condiment in Malaysia.
Keywords: Shrimp paste / Mutagenicity / Daily intake / Heavy metal / Risk assessment. .
-
-
-
Proteomics Reveals the Adverse Effects of Methyl Mercury
More LessAbstractMercury may occur naturally in the environment (mineral deposits, volcanoes, forest fires, oceanic emission, and crust degassing), or be released by human activities such as mining, mineral processing, chloroalkali production, and combustion of fossil fuels. The inorganic mercury species could be methylated in the aquatic environment. Methyl mercury (MeHg) is the most abundant and also the most toxic form of mercury in the environment. Methyl mercury is also the only mercury compound that is bioaccumulated and biomagnified in the food chain. Beluga (Huso huso) is a critically endangered sturgeon fish species that is carnivorous and feeds on benthic and pelagic fish. Because of its feeding habits, Beluga is at risk of bioaccumulating environmental contaminants. It has been reported that Beluga shows a higher concentration of mercury than other sturgeon in the Caspian Sea. In order to obtain a preliminary scope of the MeHg toxicity at the molecular level, we used a proteomics approach to analyze the changes in the brain proteome of beluga exposed to dietary MeHg. The juvenile Beluga were fed a diet containing 0.8 ppm MeHg for 70 days. Proteins of the brain tissue were analyzed using two-dimensional electrophoresis and MALDI-TOF/TOF mass spectrometry. MeHg caused a differential expression of brain tissue proteins including glycerol-3-phosphate dehydrogenase, β-tubulin, aldo/keto reductase, calmodulin, keratin 8, 70-kDa heat shock protein, aconitase, and hydrolase. These proteins are involved in metabolism, protein folding, cell division, and signal transduction in the cell.
Our results support the idea that MeHg exerts its toxicity through oxidative stress induction and apoptotic effects. They also suggest that chronic MeHg exposure would induce an important metabolic deficiency in the brain. These findings provide basic information to understand possible mechanisms of MeHg toxicity in aquatic ecosystems.
-
-
-
Lead and Cadmium Occurrence in Placenta and Associated Factors in Guiyu, China
By Shaoshan QiuAbstractToxic heavy metals are released into the environment constantly from unregulated electronic waste (e-waste) recycling in Guiyu, China, and therefore may contribute to the elevation of cadmium and other heavy metal levels in the placenta. The concentrations of heavy metals, lead (Pb) and cadmium (Cd), in human placenta from Guiyu were compared with those from a control area where no e-waste processing occurs. A total of two hundred and eighty-one placentas were collected from Guiyu (n=199) and the control area (n=82). Heavy metal concentrations were determined by graphite furnace atomic absorption spectrometry (GFAAS). Factors associated with high exposure were analyzed using Spearman Correlation Analyses. Placental cadmium (PCCd ) from Guiyu ranged from 14.21 to 376.80 ng/g with a median of 96.56 ng/g, whereas PCCd from the control area ranged from 9.71 to 51.74 ng/g with a median of 21.15 ng/g (P<0.001). No significant difference was found in placental lead (PCPb) levels between the two groups. Compared with control, the neonatal birth weight in Guiyu was significantly decreased (mean 3.15±0.03 vs 3.32±0.05, P<0.001). Spearman correlation analyses showed that the placental cadmium level showed a correlation with whether the house was used as workshop or not, the type of fuel for cooking, and milk product consumption during pregnancy. Environmental pollution, resulted from unregulated e-waste recycling activities, may contribute to elevated PCCd in neonates born in Guiyu and thus threaten their health status.
Key Words: E-waste / Placenta / Cadmium / Lead / Neonate
Shaoshan Qiu, Xia Huo, Bin Li, Junxiao Liu, Yekeen Taofeek Akangbe, Yuling Zhang, Xijin Xu
-
-
-
Cytogenetic Biomonitoring of Peripheral Blood and Oral Mucosa Cells from Car Painters
By Victor SilvaAbstractThe aim of the present study was to comparatively evaluate genomic damage and cellular death in exfoliated oral mucosa cells and peripheral blood from car painters. A total of 24 car painters and 19 health controls (non-exposed individuals) were included in this setting. Individuals had epithelial cells from cheek mucosa (left and right side) mechanically exfoliated, placed in fixative and dropped in clean slides which were checked for the above nuclear phenotypes. A total of 5uL from peripheral blood was collected for the single cell gel (comet) assay. The results pointed out significant statistical differences (p<0.05) of micronucleated oral mucosa cells from car painters. In addition, DNA damage was detected in peripheral blood cells by single cell gel (comet) assay. Nevertheless, exposure to car paints did not cause an increase in other nuclear alterations closely related to cytotoxicity such as karrhyorexis, pyknosis and karyolysis in buccal mucosa cells.
In summary, the results of the present study suggest that car painters comprise a high risk group as paints can induce genotoxic and mutagenic effects in peripheral blood and oral mucosa cells, respectively.
-
-
-
Utilizing Hormonal Effects on Intracellular Calcium to Enhance Cisplatin Anti-Cancer Actions on MCF-7 Cells
More LessAbstractWe aim to improve Cisplatin Cancer Efficacy. Cisplatin was applied to MCF7 cells pre-incubated with menstrual hormones. Intracellular calcium was measured with fluorescence microscopy and was associated with reduced cell survival in contrast to Cisplatin application only. Syncing Cisplatin administration and menstrual cycle can enhance treatment.
-
-
-
Intracellular Calcium Modulators Modulate Cisplatin-Induced Calcium Elevation in Human Breast Cancer Cells (MCF-7)
More LessAbstractCisplatin (CDDP) changes intracellular calcium concentration ([Ca2+]i) in various cell lines, while elevated [Ca2+]i induces apoptosis. We have previously shown that CDDP could elevate [Ca2+]i in MCF-7 cells. Here we investigate the source of [Ca2+]i by modulating calcium channels and transport mechanisms. Changes in the [Ca2+]i were recorded using florescence microscopy and the calcium-sensitive fluorescent dye, Fluo-4. CDDP (0.001 – 0.1 µM) and [Ca2+]i modulators, (caffeine; 10mM, nimodipine; 10M, ionomycin; 10µM, thapsigargin; 500nM, and 2-APB; 50µM) were administered to cultured MCF-7 cells via a bath perfusion system. Cytotoxicity tests were performed using MTS and FACS assays at CDDP 100pM - 10mM. Viability tests were done following 24h incubation with CDDP. CDDP induced a concentration-dependent increase of [Ca2+]i. A concentration of CDDP 0.1µM triggered the largest elevation of [Ca2+]i with a 120 percent increase (n=19). Pre-application of the calcium channel blocker, nimodipine reduced this elevation significantly (46.6 percent increase; n=26) as well as the IP3 receptor blocker 2-APB (71.4% increase; n=52). Surprisingly, when [Ca2+]i was elevated due to a pre-application of caffeine (either ionomycin or thapsigargin), the subsequent application of CDDP was also significantly reduced compared to control conditions (n=15; 37.8 percent, n=32; 34.9 percent, n=21; 53.7 percent increase respectively). CDDP concentration dependently elevates [Ca2+]i by Ca2+ entry and Ca2+ release from the stores. The pre-elevation of [Ca2+]i, through releasing Ca2+ from the stores, reduces this elevation significantly. The exact mechanisms remain unclear and further investigations are required to determine the mechanisms and pathways that are involved in the elevation of [Ca2+]i.
-
-
-
Limitations in Small Artisanal Gold Mining Addressed by Educational Components Paired with Alternative Mining Methods
More LessAbstractCurrent solutions continue to be inadequate in addressing the longstanding, worldwide problem of mercury emissions from small artisanal gold mining. Mercury, an inexpensive and easily accessible heavy metal, is used in the process of extracting gold from ore. Mercury emissions disperse, affecting human populations by causing adverse health effects and environmental and social ramifications. Many developing nations have sizable gold ore deposits, making small artisanal gold mining a major source of employment in the world. Poverty drives vulnerable, rural populations into gold mining because of social and economic instabilities. Educational programs responding to this environmental hazard have been implemented in the past, but have had low positive results due to lack of governmental support and little economic incentive. Educational and enforced intervention programs must be developed in conjunction with governmental agencies in order to successfully eliminate this ongoing problem. Industry leaders offered hopeful suggestions, but revealed limitations when trying to develop encompassing solutions to halt mercury emissions. This research highlights potential options that have been attempted in the past and suggests alternative solutions to improve upon these methods. Some methods include buyer impact recognition, risk assessment proposals exposing a cost-benefit analysis and toxicokinetic modeling, public health awareness campaigns, and the education of miners, healthcare workers, and locals within hazardous areas of mercury exposure. These methods, paired with the implementation of alternative mining techniques, propose a substantial reduction of mercury emissions.
-
-
-
An Alternative Mechanism for Melatonin’s Protective Effects on Metal Ion Toxicity – Modulation of pro-/anti-apoptotic Proteins
More LessAbstractOur objective was: Does Melatonin protect against cisplatin (Pt(II)) toxicity by a mechanism that is not free radical based? We used, flow cytometry, cell-viability, immunoblotting, and immunofluorescence, to determine the following: Cisplatin induced apoptosis is reversed by melatonin at physiological concentrations by localization of Bcl-2 and down regulation of Bax, besides reduction of oxidative stress.
Vignesh Shanmugam*, Amro Wafi, Elizabeth Varghese and Dietrich Büsselberg, Weill Cornell Medical College in Qatar
-
-
-
Genetics of Dyslipidemias and the Role of the ApoE Arg145Cys Mutation in African-derived Populations
More LessAbstractDyslipidemia is a complex phenotype that depends on gene-environment interactions to be manifested. Deleterious mutations in proteins of the lipid transport pathway are expected to contribute to dyslipidemias. Apolipoprotein E (ApoE), a protein component of blood lipid particles, plays an important role in lipid transport and delivery. Single polymorphisms in residues 112 and 158 define the common E2, E3 and E4 alleles. In a study of Qataris, we observed that 17.4 percent of the African-derived genetic subgroup were heterozygotes for the rare Arg145Cys (R145C) variant that functions as a dominant trait with incomplete penetrance associated with dyslipidemia. Based on this, we hypothesized that the R145C polymorphism may be common in African-derived populations. The prevalence of the R145C variant worldwide was assessed in the 1000 Genomes Project (1000G) and then in 1012 Caucasians and 1226 African-Americans in New York City. Lipid profiles of the Qatari and New York R145C+ heterozygotes were compared to controls. R145C+ Qatari heterozygotes had higher triglyceride levels compared to Qatari controls (p<0.007). The 1000Gs data demonstrated that the R145C polymorphism is rare in non-African derived populations, but present in 4.9-12.3 percent of sub-Saharan African-derived populations. The R145C polymorphism was rare in New York City Caucasians (1/1012, 0.1%), but strikingly, 53 (4.3 percent) of 1,226 New York City African-Americans were R145C+ heterozygotes, with an average of 52 percent higher fasting triglyceride levels compared to African-American R145C- controls (p<0.002).
Based on these observations, there are likely to be millions of people worldwide derived from sub-Saharan Africans that are ApoE R145C+. While larger epidemiologic studies will be necessary to determine the long-term consequences of this polymorphism and the environmental and genetic factors contributing to severe manifestation of dyslipidemia in a subset of carriers, the available evidence suggests it is a common cause of triglyceride dyslipidemia.
Maen D. Abou Ziki, Yael Strulovici-Barel, Neil R. Hackett, Juan L. Rodriguez-Flores, Jason G. Mezey, Jacqueline Salit, Sharon Radisch, Charleen Hollmann, Lotfi Chouchane, Joel Malek, Mahmoud A. Zirie, Amin Jayyuosi, Antonio M. Gotto, Jr, and Ronald G. Crystal
-
-
-
Lactase Persistence Variants as Markers to Study Human Demographic Movements in the Light of Animal Domestication and Milk Culture
More LessAbstractPersistence or non-persistence of lactase expression into adult life is a polymorphic trait that has been attributed to a single nucleotide polymorphism (-13910 C>T) in an enhancer element 13.9 kb upstream of the lactase gene (LCT). Recent studies have demonstrated that lactase persistence (LP) variants -13910*T and -13915*G have emerged from different allelic backgrounds and occur at very high frequencies in different populations. Iranian and Arabian populations have been reported to differ significantly in genetic patterns at these LP variants. The Arabian population is characterized by a 50-60 percent frequency of a -13915*G allele, attributable to its consumption of camel milk. This allele has not been detected so far among the Iranian population which, on the contrary, is similar to the European and Near Eastern populations showing a moderate frequency of -13910*T allele, which occurs at a significantly lower frequency in Arabia. In this background, we intended to determine the putative genetic source for the Indian Muslim population as mtDNA and Y chromosomal markers showed relatively low levels of genetic differentiation between their two potential sources of origin, Iran and Arabia. We sequenced for a 400 bp fragment around -13910 region of the LCT gene in 747 individuals from different regions of India. The variant -13910*T was widely observed in both Indian Muslim (Indian Shia-10 percent Indian Sunni-10 percent Dawoodi Bohra (TN)-14 percent, Dawoodi Bohra (GUJ)-11 percent, Mappla-2 percent, Iranian Shia-4 percent), and non-Muslim populations (North India-19 percent, West India-23 percent, South India-10 percent). The Iranian population also exhibited the same mutation with 10 percent frequency. The Arabian-specific -13915*G variant was completely absent from the Indian population, yet at the same position a new -13915*C variant (Mappla-1percent and South India-1 percent), likely to be an Indian-specific mutation was observed. The wide spread of the LP variant -13910*T among the Indian Muslim populations examined excludes the possibility of major genetic input from Arabia and corroborates the gene flow primarily from Iran, rather than directly from the Arabian Peninsula. Thus, the LCT gene correlating with LP in humans reveals the convergent evolution of the LP in diverse populations, most probably reflecting different histories of adaptation to milk culture and cattle domestication.
Muthukrishnan Eaaswarkhanth, Irene Gallego Romero, Toomas Kivisild, Kumarasamy Thangaraj
-
-
-
Towards On-The-Spot Analysis: Population Proteomics of European Hake
More LessAbstractNumerous leaders in fisheries science highlight the need for improved governance of our oceans, especially in relation to Unreported and Unregulated Fishing (IUU) activities. The global impact of the ongoing and relentless loss of fish biomass, biodiversity and fisheries income adds, not only considerable uncertainty to our forecasts of sustainability, but also there are concomitant threats to ecosystem function, food security and the economic and social viability of fishing communities. In this context, population proteomics is becoming a powerful tool enabling the study of the population structures and functional adaptations to environment from human settlement to animal natural populations. A proteome scan approach based on two-dimensional fluorescence difference gel electrophoresis (DIGE) technology has been applied to generated thousands of protein markers that allow the identification of different hake (Merluccius merluccius) population, a species of most important interest to fisheries and human consumption. Based on quantitative differential analysis of hake populations, several protein markers were selected that reliably assigned individuals to the populations of origin. These new methods have the potential to complement, and in some cases, even supplement more established approaches, as they rapidly respond to the environment where the fish was living just prior to capture, and therefore provide information on geographic origin, etc.
-
-
-
Constraints of Efficient Waterborne Disease in Sudan with Special Emphasis on Malaria
More LessAbstractThe shortcomings in water quality and sanitation in Sudan are directly reflected in the incidence of waterborne diseases, which make up to 80 percent of reported diseases in the country. The incidence of disease is highly seasonal: the greatest problem usually occurred at the start of the wet season as the rains and runoff mobilize the faecal matter and pollutants that have accumulated during the dry season. Apart from the routine waterborne illness such as cholera, dysentery, hepatitis A and a range of parasitic infections like schistosomiasis, a number of tropical diseases including malaria, sleeping sickness, river blindness etc are prevailing in Sudan. This paper aims to identify the factors responsible for inefficient control of waterborne diseases in Sudan with special emphasis on malaria in Sudan ie factors other than diagnosis and medication. The methodology adopted was very simple and straightforward based on the fact that, irrespective of the improvement in diagnosis and treatment of waterborne diseases, 80 percent of reported diseases in Sudan were diseases transmitted by water. These factors were identified and analyzed using network analysis which is one of the most famous environmental impact assessment (EIA) methods. It uses a cause and effect relationship to link different factors and helps to identify primary, secondary, and tertiary impacts the inefficient control of malaria resulted from natural, as well as, man-made factors. Natural (environmental) factors include climate, topography, soil type, and vegetation. While the most important factors among the man-made group includes: ill-planning, irrelevant land use, conflicts and displacement, irrational expansion of settlements, poor environmental awareness, inefficient liquid waste management, leakage of domestic water supply networks and poor infrastructure etc. The main conclusion is that medical treatment is not the sole factor for the efficient control of the incidence of malaria disease in Sudan. Natural and man-made factors should be accompanied by the eradication or reducuction of the negative health impacts of the prevalence of malaria disease. Efficient control of malaria can be achieved through the improvement and regular maintenance of domestic water supply networks, by upgrading wastewater treatment plants, raising awareness, and adopting measures that reduce the accumulation of stagnant water.
Keywords: Waterborne diseases / Malaria / Environmental impact assessment / Wastewater treatment plants.
-
-
-
Lifestyle and Air Pollution: The use of Domestic Generators in an African City
By Ahmad YahyaAbstractAir is doubtlessly a basic necessity without which no living being can survive. The sole function of the breathing mechanism in human beings is the taking in of needed air (oxygen) and pushing out unneeded air (carbon dioxide). The need for clean and unpolluted air should therefore not be over-emphasized. With the debut of modern technology, man-made air pollution is gradually becoming a dominant trend. Human-induced carbon monoxide emission is posing a chronic threat to the well-being of, not only humankind, but the entire flora and fauna worlds. One of the chief sources of this dangerous substance in developing countries, particularly Africa, is domestic generators. This paper looks at the lifestyle of people in the Nigerian city of Kano, an arid zone, with a view to determining the extent to which they are attached to domestic generators, and the resultant carbon monoxide emission. Randomly sampling residences in Kano Metropolis, the paper attempts to find out the number of those who use domestic generators, the frequency of their use, the average number of hours for which these generators are working and, if possible, the amount of carbon monoxide emitted within this timeframe along with the level to which this pollutes the air, and the consequent health hazards that this entails. The paper discovered that the number of residents in Kano Metropolis who own, and constantly use domestic generators, exceeds that of those who do not. The paper also found out that the aspects of lifestyles which strongly attached them to the constant use of domestic generators include: organized feasts, lighting mosques, schools and Majalis, voluntarily lighting streets and neighbouring houses, and working within residential areas. The paper also discovered that most of the generators are in operation for longer, and their combined emitted carbon monoxide is highly voluminous which can substantially cause health hazards by polluting the air. The paper concludes that lifestyle plays a significant role in air pollution as reflected in Kano Metropolis and there is therefore the need for moderation and regulation to eschew this menace.
Keywords: Lifestyle / Africa / Kano / Generators / Pollution
Ahmad Yahya, Department Of Islamic Studies, Federal College Of Education, Pmb 3045, Kano, Nigeria
EMail: [email protected]
-
-
-
Spatial Distribution of Mental Retardation in Iran
By Ali GoliAbstractMedical geography applies the theory, methods and analysis tools of geography science to the study of human health, disease and health care systems. As the Geographic Information System (GIS) has evolved since the mid-twentieth century, its uses have spread in geographic-related knowledge. Medical geography also uses GIS in the study and analysis of health and diseases researches. Mental retardation (MR) is a subset of developmental delay (DD), a broader classification of childhood disability. Spatial analysis is useful for the identification of areas with MR people. Identification of clusters based on MR provides an important tool to investigate risk exposures. However, even though MR is a substantial public health problem, there are no previous analyses of spatial clustering of MR using individual case data. In this paper, we examine the use of the spatial analysis approach in the analysis of MR clustering. We used data from the 2006 census, which addresses the amount of MR data available on a county level. MR cases with unknown causes were identified in the study population. Local statistic indices were used to identify spatial clusters of MR, the corresponding P-value for each geo-coded location, and the P-value surface contoured as a heat image to identify the MR clusters. The characteristics of the study population were analyzed using Moran's I value and Getis-Ord Gi statistic and the results confirm that clustering does occur for MR. The shapes of the identified MR clusters were found in counties with a high illiteracy percentage. Also MR cluster were discovered in counties with a high rate of residence in rural areas.
Keywords: Mental retardation / mMedical geography / Spatial analysis / Local statistic indices / Spatial cluster.
Ali Goli, Assistant professor, Sociology and Social Planning Department, Social Science Faculty, Shiraz University, Shiraz
EMail: [email protected]
-
-
-
Response of Ficus nitida plants to Mycorrhizal Fungi, Ascorbic Acid and Fe- EDTA for Decreasing the Harmful Effect of Lead Pollution
More LessAbstractThis study was carried out at the Floriculture Nursery of the Ornamental Horticulture Department, Faculty of Agriculture, Cairo University during 2005-2007 to investigate the effect of some treatments on Ficus nitida plants grown in polluted soil with Pb. Lead concentrations in soil (0, 500, 1000, 2000 ppm) in 1st stage and (0, 500, 2500, 5000 ppm) in 2nd stage caused changes in growth characters and chemical composition of Ficus nitida plants. Decreases in plant height, root length, branch numbers, leaf numbers and leaf areas, as well as fresh and dry weights of shoots and roots, were obtained in the two different stages of growth. Also, lead caused decrement in chl.a, chl.b, total carotenoids, catalase activity and micronutrients concentration, while increment in total sugars, total soluble phenols and free amino acids concentration, as well as peroxidase and Superoxide dismutase (SOD) activity, were recorded in plant leaves under lead treatment compared with control in the two stages. On the other hand, a reverse trend in two stages was recorded by the plants treated with mycorrhiza fungi (500 and 1,000 spores) soil addition, Fe-EDTA (130 and 260 ppm) and ascorbic acid (250 and 500 ppm) foliar application under lead soil pollution. These treatments, can overcome, to some extent, the hazard effect of lead on Ficus nitida plants.
Key words: Fe- EDTA / Ficus nitida / Lead / Mycorrhizal fungi / Ascorbic acid.
Dr Abdullah Hussein Tahish, Forests and Horticulture Department—Faculty of Agriculture, Sana'a University
-
-
-
Treatment of an Endocrine Disruption Pesticide by Microbial Biodegradation Process
More LessAbstractPesticides are widely used in agriculture to control a variety of pernicious organisms that spoil the crops. Nevertheless, low amounts of some residues may persist in the food supply, air, water and soil and could constitute a significant hazard pathway for humans. Most pesticides are classified by the World Health Organization as hazardous, and several widely used pesticides are known as potential Endocrine Disrupting Chemicals by the US Environmental Protection Agency (EPA). Bifenthrin insecticide, widely used in agriculture, constitutes a major environmental problem, because of its high toxicity and its persistence in the environment. It is now well established that Bifenthrin interferes with the action of female sex hormones, causing reductions in ovary weight and lack of oestrus and it decreases the level of thyroid hormones present in the blood. Bioremediation is a pollution control technology that uses biological systems to catalyze the degradation or transformation of various toxic chemicals. The present study involves the isolation of bacterial and fungal cultures metabolizing bifenthrin pesticide from soil having previously exposed to the pesticide. The biodegradation of bifenthrin insecticide was studied using these indigenous isolated fungi (Aspergillus niger and Rhizopus stolonifer) and bacteria (Aeromonas sp and Pseudomonas aeruginosa). The biodegradability was evaluated by the manometric respirometry test (OECD method 301F). The results showed that the evolution of biomass, biological oxygen demand (BOD) and chemical oxygen demand (COD) can highlight the biodegradation phenomenon. Maximum degrading potential was revealed by the fungi strains Aspergillus niger with 82.5% and Rhizopus stolonifer with 73.7% against 6 to11% for bacteria. The determined factorial design model successfully described the bifenthrin biodegradation phenomenon by the studied fungi. Therefore, the fungal strains might be useful for bioremediation of this endocrine disruption pesticide-contaminated environment.
Keywords: Endocrine disruption pesticide / Bifenthrin / Microbial biodegradation.
-
-
-
No Oxidative Stress or Genotoxicity in Patients under Isoflurane or Propofol Anesthesia
More LessAbstractOxidative stress is characterized by the imbalance between reactive oxygen species (ROS) generation and antioxidant production. It is known that ROS can cause DNA lesions, which may be related to mutagenesis and carcinogenesis. However, little is known about the lipoperoxidation, antioxidant capacity and oxidative DNA damage in patients undergoing inhaled anesthetic isoflurane (ISF) or the intravenous anesthetic propofol (PF) during surgical procedure. This study aimed to evaluate the effects of isoflurane and propofol anesthesia on DNA, lipoperoxidation and on the antioxidant capacity in patients undergoing elective surgery lasting at least 120 minutes. The Ethical Committee of the Institution approved the protocol of the study, which included 30 adult patients (both genders, 18-50 years old) classified by the American Society of Anesthesiologists (ASA) as physical status I (healthy patient with no disease other than a surgical abnormality), and who were scheduled for otorhinological surgery. Patients were randomized to receive general anesthesia with propofol (n=15) or isoflurane anesthesia (n=15). Blood samples were drawn before anesthesia (T1-baseline) and 120 minutes after the beginning of anesthesia (T2). Lymphocytes were isolated and comet assay was performed using OGG1 enzyme to detect oxidative DNA damage. Both malondialdehyde (MDA), which is a potential biomarker of oxidative stress (one of the end products of lipoperoxidation), and hydrophilic antioxidant capacity were evaluated in plasma by using a fluorescent plate reader. Despite an increased hydrophilic antioxidant capacity during anesthesia in both groups (ISF and PF), and decreased amount of oxidative DNA lesions at T2, differences between T1 and T2 were not statistically significant. Also MDA levels did not change between T1 and T2 moments or between the groups. In conclusion, none of the anesthetics (propofol or isoflurane) led to oxidative stress or caused oxidative DNA damage in ASA I patients undergoing surgical procedure.
Financial support: FAPESP (grant number 2010/05611-0) Salvadori DMF1, Braz MG1, Freire CM1, Braz LG2, Ferreira ALA3, Braz JRC2
-
-
-
Evaluation of Genotoxicity of Medicaments in Sick Patients
More LessAbstractThe aim of this study was to evaluate the genotoxicity of medication in bucall cells, used in chemotherapy of sick patients with lung cancer. Following chemotherapy treatment, samples were taken five, 10 and 15 days afterwards, with cytobrush, and placed in a ringer solution. Samples were taken from 30 patients suffering from lung cancer; The control group consisted of 30 subjects. A high frequency of micronuclei in exfoliated bucall cells were found after treatment wih medication, but they were not statistically significant. According to this result, we can conclude that chemotherapy induces the micronuclei in bucall cells of patients lung cancer.
Keywords: Genotoxicity / Medicaments / Hospital / Lung
Kemajl Kurteshi, Kasum Letaj, Muharrem Ismaili, Zeqir Shaqiri
-
-
-
In Vitro Cancer Chemopreventive Properties of Polysaccharide Extract from the Brown Alga, Sargassum Latifolium
By Mona AbozeidAbstractPolysaccharides of edible algae attracted extensive interest due to their numerous biological activities. Sargassum latifolium (Turner) C. Agardh, belongs to Sargassaceae, is —a brown algae found in Egyptian Red Sea shores. This work is a novel attempt to explore the cancer chemopreventive activity of different fractions of water-soluble polysaccharide extract derived from S. latifolium. Estimation of cancer chemopreventive activity, specifically anti-initiation, including the modulation of carcinogen metabolism and the antioxidant capacity, revealed that E1 and E4 were potent anti-initiators, where they lead not only to an inhibition in the carcinogen activator cytochrome P450 1A (IC50 2.54 and 10.30 µg/ml, respectively), but also to an induction in the carcinogen detoxification enzymes glutathione-S-transferases (144 percent and 225 percent of the control, respectively). E1 and E4 inhibited 59 percent and 63 percent of the induced-DNA damage, as measured by comet assay. Similarly both E1 and E4 possessed potential anti-promoting properties as indicated by their anti-inflammatory activity. E1 and E4 enhanced the macrophage proliferation; however they dramatically inhibited the stimulated NO (30.7percent and 59.3 percent), TNF-a (38.2 percent and 54.9) and COX-2 (20 percent and 18 percent), respectively. E3 showed a selective cytotoxicity against lymphoblastic leukemia (1301 cells), while other fraction extracts had no cytotoxic effect against all tested cell lines. E3 led to a major disturbance in cell cycle including arrest in both S-phases in 1301 cells. This disturbance was associated with an induced-cell death due to apoptosis, but not necrosis.
In conclusion, E1 and E4 are promising cancer chemopreventive fractions, since they had tumor anti- initiating activity via their protective modulation of carcinogen metabolism, and tumor anti-promoting activity via their anti-inflammatory activity, while E3 can be considered as a promising anti-cancer agent against leukemia.
Keywords: Sargassum latifolium / Cytochrome P450 / Cancer chemoprevention / Anti-initiating / Anti promoting / Apoptosis.
Amira M. Gamal-Eldeen a, Eman F. Ahmed b, Mona A. Abo-Zeid c
-
-
-
Antagonistic Role of Selenium against Hepatotoxic Effects of Nicl2 in Preimplanted Wistar Albino Rats
More LessAbstractNickel, a potent toxic metal, is very harmful to the environment and to humans because of its in vivo accumulation in liver. The present study was conducted to investigate the protective effect of selenium (Se) against nickel toxicity on liver function in preimplanted Wistar albino rats. NiCl2 was given on day three of pregnancy either in distilled drinking water at a dose of 20 mg/L/day) for 16 consecutive days or as a single s.c. dose of 25, 50, or 100 mg/kg. Se was given as an s.c. injection (0.3 mg/kg) together with the higher dose (100 mg/kg) of NiCl2. Changes in plasma glucose, triglycerides and total cholesterol were measured in treated and control groups on days five and 20 of gestation. NiCl2 s.c. induced on day five of gestation showed a significant (<0.05) decrease in plasma triglycerides, with a dose of 100 mg / kg (-48 percent). This decrease was maintained at day 20 of gestation with doses of 50 mg / kg (-36 percent) and 100 mg / kg (-31 percent). In contrast, the low dose induced an increase of + 50 percent in plasma triglyceride compared to controls. In addition, NiCl2 s.c. caused on day five of gestation a significant decrease (p <0.05) in plasma total cholesterol with the low (-50 percent) and medium doses (-26 percent). However, the dose of 100 mg / kg induced a significant increase (114 percent) in plasma total cholesterol on day 20 of gestation compared to controls. NiCl2 s.c. induced a significant increase in plasma glucose (+125 percent) on day 20 of pregnancy. The pretreatment with Se counteracted the effects of NiCl2 on plasma glucose, total cholesterol and triglycerides.
NiCl2 administered in the drinking water induced a significant increase (<0.05) in plasma triglycerides (+68 percent) and cholesterol (+49 percent) on day 20 of gestation, while on day five of gestation NiCl2 s.c. induced a significant decrease in cholesterol (-31 percent) compared to controls. All doses of NiCl2 induced an alteration of liver architecture. Co-administration of Se with NiCl2 restored the structure of the liver.
These results suggested that selenium has a hepatoprotective role against the toxicity induced by NiCl2 administered subcutaneously in preimplanted rats. .
-
-
-
Health Hazards faced by Women Beedi Rollers
More LessAbstractHealth problems of 197 female beedi rollers were studied in Patna, Bihar, India to ascertain the effects of beedi rolling on hematological parameters, liver function and on the eyes, respiratory, gastrointestinal and nervous systems. The study found that more than 70 percent of the beedi rollers suffered from eye, gastrointestinal and nervous problems while more than 50 percent of the respondents suffered from respiratory problems, mostly throat burning and cough. More than 75 percent of the respondents faced osteological problems. Total RBC, WBC and platelet counts of the beedi rollers were significantly lower in comparison to the control subjects. Differential leucocyte count showed significantly risen lymphocytes and eosinophils and lowered neutrophils and monocytes in the beedi rollers as compared to the control group. Hemoglobin levels were lower among beedi rollers compared to the control group. SGPT (ALT) enzyme concentration, a parameter of liver dysfunction, was significantly increased in the beedi rollers compared to the control group. The study revealed that women beedi rollers face numerous health problems possibly due to direct inhalation of tobacco flakes and dust. .
-
-
-
Preference of Human Biological Samples for Exposure Assessment of Elemental Pollution and Health Implication
More LessAbstractThe compounds of nickel, arsenic, cobalt, beryllium, thallium, aluminum, lead, mercury, zirconium and cadmium exert pronounced comutagenic effects, by disturbing DNA repair and interfering with base and nucleotide excision repair. These elements can be widely dispersed throughout the environment as a result of fossil fuel combustion, industrial and agricultural processes and natural processes. The potential mobilization of these toxic trace metals and metalloids in our environment, pose health hazards, in particular, children exposed to metals are more susceptible to DNA damage. A number of human samples: hair, nails, blood, urine, teeth, saliva, perspiration, milk and semen were analyzed for levels of trace elements to compare with the presence or absence of micronuclei in peripheral blood leucocytes and disturbances of DNA repair systems. The ranges of lead, nickel and cadmium are found in urine, blood, teeth, hair and nails of general subjects from Mysore, India, and the absence of micronuclei levels in their peripheral blood samples, indicated that the elemental levels were below the threshold limit and that there is a need for reference values of these elements measured in the biosamples with the micronuclei assessment for confirmation and assurance. The literature was reviewed, and the reference values of mutagenic elements for biosamples was presented and discussed. .
-
-
-
Elevated Serum Polybrominated Diphenyl Ethers and Alteration of Thyroid Hormones in Children from Guiyu, China
By Junxiao LiuAbstractOur objective was to explore the thyroid hormones (TH), and problems related to polybrominated diphenyl ether (PBDE) flame retardants exposure in children in an electronic waste recycling town of Guiyu. We determined blood PBDE levels, by gas chromatography coupled with mass spectrometry, in 145 children, aged four to six years old, from Guiyu, China. Three THs were also measured. The geometric mean (95 percent CI) of the total PBDE (∑PBDE) was 162.98 (141.25-186.21) ng/g lipid for Guiyu children. The concentration of ∑PBDE exceeded 100ng/g lipid of Guiyu children was 79 percent (115 children). The serum free T3 (median 5.73, range 3.80-7.71 pmol/L) and serum free T4 (median 15.91, range 8.89-22.45 pmol/L) in high PBDE exposure group (300.1-583.0 ng/g lipid of ∑PBDEs) were lower than in the control group (0-100.0 ng/g lipid of ∑PBDEs), and thyroid-stimulating hormone (TSH) in high PBDE exposure group was higher than in the control (all P< 0.05). The TH levels were correlated with most of the PBDE concentrations. Residence adjacent to e-waste workshops, as determined by the questionnaire, was an independent predictor of the free T3 levels, and the house as a family workshop was a significant predictor of the free T4 (all P<0.05). Residence adjacent to e-waste workshops and the house as a family workshop were associated with serum TSH (all P< 0.05). These results suggest that elevated child PBDE levels in Guiyu, may threaten child health, with implications for altered child TH levels, due to informal e-waste recycling activities.
Junxiao Liu, Xijin Xu, Yuanping Wang, Qiongna Xiao, Xia Huo .
-
-
-
Water Sanitation and Hygiene Correlation with Human Health Problems in Georgia
More LessAbstractAccess to safe drinking water and sanitation is essential for the protection and promotion of health. It is a basic human right, and a key component of an effective public health delivery system. The importance of community water supply and sanitation as a key health and development issue, has been highlighted in a number of international policy forums in Georgia. In terms of priority environmental conditions, diarrhoea and dysentery still constitute major health problems for some villages. The study conducted by AFRD attempted to gauge the perceptions and level of awareness of the respondents on the following issues to assess the impact on the personal hygiene practices and overall health and disease burden on the following issues: upkeep of personal hygiene, safe storage and handling of drinking water, home and food sanitation, safe disposal of human excreta, safe disposal of solid wastes, safe disposal of liquid wastes, sanitation in the community. An attempt was made to measure the perceptions and level of awareness by questions defining each of the issues mentioned above. In order to analyse the overall trend, a public health awareness score was worked out for all the sample respondents.
Dr Kakha Nadiradze, President AFRD, Mrs. Nana Phirosmanashvili, Researcher AFRD Association for Farmers Rights Defense, AFRD email; [email protected] .
-
-
-
Pesticides as an Environmental Health Risk Factor in Children Living in Agricultural Areas - Exposure Science in Public Health
More LessAbstractThe seasonal accessibility and stability of pesticides by spreading and/or decomposing result in the migration and deposition of these products to all elements of the environment. In the context of a complex, multi-factor chemical hypersensitivity, the presence of pesticides in the environment and their long-term negative effects is an important factor in the health condition of the population living in areas of intensive pesticide use. Aside from the adult population, the rural child population is especially exposed. The constant exposure of children to even low concentrations of pesticides may lead to permanent health disorders and limits to their development. A child’s exposure already starts during the prenatal period of development, when toxic substances, including pesticides and their metabolites penetrate through the placental barrier into the foetus, which may inhibit intrauteral growth and contribute to the reduction in the duration of pregnancy or lower birth weight. Children absorb toxic substances via the respiratory and alimentary route more easily than adults, discharge xenobionts cumulated in the body more slowly, have a quicker pace of metabolic change, and their physiology is constantly developing. Therefore, it is advisable to evaluate the effect of environmental exposure of pesticides to children living in areas where there is intensive use of plant protection products. Key words: Pesticides / Environmental Exposure / Children / Biomarkers
LUCYNA KAPKA-SKRZYPCZAK, MAŁGORZATA CYRANKA, MACIEJ SKRZYPCZAK, MARCIN KRUSZEWSKI .
-
-
-
Environmental and Occupational Health Impacts for Tobacco Cultivation: A Case Study on a Developing Country (Bangladesh)
More LessAbstractBangladesh is an agriculture-based country. However, nowadays, tobacco cultivation has increased significantly (about 65 percent) in the last few years compared to other cereal crops. Tobacco cultivation has an impact not only by its production but also by its processing. The overall impact of tobacco cultivation is negative, considering the environmental and occupational health measures and indicators. The environment is damaged due to the overuse of pesticides and fertilizers, tobacco processing; and occupational health is in a vulnerable state due to the dispersal of harmful substances emitted during tobacco processing. The social impacts are significant, and respiratory and lung diseases are now obvious to the tobacco farmers and their families. Social surveys were conducted at the tobacco cultivation sites to identify the social and environmental impacts of tobacco cultivation. In this study, an assessment of environmental and occupational health impacts due to tobacco cultivation and processing were highlighted considering the health issues. A risk assessment framework was suggested considering the social and environmental dynamics of tobacco cultivation in different areas of Bangladesh.
Keywords: Environment / Health / Impacts / Occupational / Tobacco
Shahriar Rahman, Environmental and GIS Specialist, International Union for Conservation of Nature (IUCN), Bangladesh Country Office, House # 11, Road # 138, Dhaka-1212, Bangladesh EMail: [email protected] .
-
-
-
Study of Oral Health Among Workers in the Field of Radiation
More LessAbstractThis study was designed to investigate the characteristics of oral conditions of workers in a radiation field. The study was carried out on male subjects with ages ranging from 25-45 years and working in the National Center for Research and Radiation Technology (NCRRT), under protective measures and subjected to long-term low dose ionizing radiation. The subjects were divided into four groups; the first three groups represented the study groups, including subjects working in the radiation field; and a fourth group, the control group, including subjects working away from the radiation field. Study groups were divided according to the duration of work into the first group (including 20 subjects working for at least 10 years), the second group (including 20 subjects working from 5-10 years and the third group (including subjects working for at least five years). The investigation in bothstudy and control groups was made via immunological assessment by determination of the level of secretory immunoglobulin A (SIgA), microbiological assessment via detection of aerobic, anaerobic bacteria and Candida albicans and by dental assessment through determination of dental indices (Decayed Missed –Filled (DMF) index, periodontal index and Plaque index). The results of this study reported lower level of SIgA in study groups compared to controls and the presence of Actinobacillus-actinomycetemcomitans, Fusobacterium and Bacteriod Forythus in study groups. There was a significant difference between the study and control groups regarding DMF index, periodontal index and Plague index, in addition to the negative correlation between SIgA and the dental índices. This study showed that workers in the radiation hall NCRRT, subjected to long-term low dose ionizing radiation, were found to be at higher risk of carying and periodontal diseases compared to the control group.
Hala I Awadalla, Radwa A sallam, Mohamed G. Haggag, Abd El Monem S.Bashandi, Khaled A Abd El Khaffar .
-
-
-
Antimutagenic Polyphenols in African Foods
More LessAbstractPolyphenols are ubiquitous in plant foods, and many have been associated with a variety of biological activities, including antimutagenic and anticarcinogenic properties. Some African foodstuffs have been analyzed for antimutagenic polyphenols by High-Performance Liquid Chromatography–Electrospray Ionization–Mass Spectrometry (HPLC-ESI-MS). The results showed that Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives. Also Canarium schweinfurthii Engl oil contained phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol. In addition, tomatoes (Lycopersicun esculentum Mill) contained the powerful antioxidant, lycopene; cabbage (Brassica oleracea) contained indole-3-carbinol; citrus fruits contained pectin; Soursop (Annona muricata) contained annonaceous acetogenins; soya beans (Glycine max) contained isoflavones; chilli pepper (Capsicum annuum) contained capsaicin, and green tea (Camellia sinensis) contained (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate. Considered together with the reported presence of antimutagenic polyphenols, especially flavonoids in other African foods like bitter leaf (Vernonia amygdalina), red palm oil (Elaeis guineensis), Hibiscus sabdariffa), okra (Hibiscus esculentus), Beniseed (Sesanum indicum), Adansonia digitata, Amaranthus sp, Telfeiria occidentalis, locust beans (Parkia clapertoniana), ginger (Ginger officinale), garlic (Allium sativum), Tamarindus indica, cashew (Anacardium occidentalis), Mango (Mangifera indica), Vitex doniana, Syzygium aromaticum, Balanites aegyptiaca, citrus fruits, Irvingia gabonensis, Psidium guavjava, Talinum triangulare, Garcinia cola, tomatoes, soya beans, atile (Canarium schweinfurthii), it is concluded that a number of African foods have the capacity to mitigate against mutation induced by several environmental agents, and therefore could contribute significantly to cancer chemoprevention.
S.E. Atawodi, Biochemistry Department, Ahmadu Bello University, Zaria, Nigeria EMail: [email protected] .
-
-
-
Antimutagenic Polyphenols in African Foods
More LessAbstractThe major problem with cancer is the ability of cancer cells to infiltrate surrounding tissue (invasion) or to spread to distant organs (metastasis), thereby decreasing the patient’s survival. One of the first steps in the process of metastasis is local spreading or invasion from the primary tumour and certain Ca2+ -binding proteins of the S100 family eg, S100A4 and S100P, can induce a metastatic phenotype and enhance cell migration and invasion. Both S100A4 and S100P are expressed at elevated levels in several forms of cancer including breast, pancreatic, prostate, colon, ovary, oesophagus and lung cancer. Initially, we introduced a series of deletion mutants on the S100A4 protein by truncation of the C-terminal region. The S100A4 open-reading-frame cloned into an expression vector was subjected to site-directed mutagenesis to create the mutations, either by deletion or by substitution. These mutant proteins, when expressed in cells, conferred reduced metastasis, invasion and migration-inducing abilities, compared to cells expressing wild type S100A4 protein. The mutations reduced the ability of the S100A4 protein to bind to one of its intracellular targets, non-muscle myosin II heavy chain isoform A (NMMHCIIA) in vitro. There was a significant reduction in metastasis, migration and binding to NMMHCIIA when only the last two basic C-terminal lysine residues (Lys100, 101) were removed. A similar decrease in metastasis, migration, and invasion was also observed in mutated S100P protein. Removing the single C-terminal lysine residue from S100P protein, or its replacement by alanine, dramatically reduced the metastasis-promoting ability of this protein. Binding to NMMHCIIA was also tested in vitro. The results showed that S100P mutant protein exhibited 10-folds lower affinity to NMMHCIIA than to the wild type protein. In vivo, cells expressing high levels of S100P mutant protein exhibited a dramatically changed organisation of the NMMHCIIA cytoskeleton compared to cells expressing wild type S100P. There was also change in the actin cytoskeleton to a more polarised, highly bundled structure in cells with an elevated level of mutant S100P protein compared to cells expressing the wild type protein. These results identify the lysine(s) at the C-terminal of these two S100 family proteins as being important in their binding to one of their target proteins, in cell migration, cytoskeletal organisation, cell invasion and metastasis. These observations may have pharmaceutical implications for potential anti-cancer drugs targeted to S100A4 and S100P. This work was supported by the James Tudor Foundation and the Cancer and Polio Research Fund.
Thamir Ismail, Stephane Gross, Connie Goh, Mark C. Wilkinson, Philip S. Rudland and Roger Barraclough .
-
-
-
Detection of HPV DNA (16 and 18) in Squamous Cell Carcinoma of the Tongue by Polymerase Chain Reaction
More LessAbstractHuman papilloma virus (HPV) is one of the important causal agents of gynecological cancers which appears to play an important role in cancer of the oral cavity and oropharynx. This study evaluates the relationship between the presence of HPV and squamous cell carcinoma (SCC) of the tongue in nonsmokers in south Iran. In this case-control study, pathologic specimens of 35 nonsmokers with a histological diagnosis of tongue SCC, compared with 30 specimen from patients with tongue lesions other than intraepithelial neoplasms. Polymerase chain reaction (PCR) was used to detect HPV16 and 18 genome in both groups. 10 out of 35 in the case group and one out of 30 in the control group, 28.5 percent versus 3.3 percent, showed the presence of the HPV genome by use of PCR. Chi-square test used for statistical analysis of data (p value=0.007). Nevertheless, the present study supports the strong association between HPV infection and tongue SCC in non-smokers. Tongue SCC is known as a rare disease, so the planning for more advanced studies to confirm this association and the use of proper HPV vaccination is strongly suggested; particularly when an increase of oro-genital practice worldwide increases the incidence of tongue SCC. .
-
-
-
Adaptive Response in a Population Exposed to High Levels of Air Pollution
More LessAbstractWe investigated the impact of air pollution on individuals living in the heavily polluted industrial Ostrava region and compared it with individuals from the relatively clean capital city of Prague, Czech Republic. The study was conducted in three sampling stages, differing in the concentrations of air pollutants (winter 2009, summer 2009 and winter 2010). In all stages the study subjects from the Ostrava region were exposed to significantly higher concentrations of benzo[a]pyrene (B[a]P) and benzene than the subjects in Prague. To evaluate DNA damage in subjects from both locations we detected levels of bulky DNA adducts, chromosomal aberrations and micronuclei in peripheral blood lymphocytes, and oxidative stress markers in blood plasma and urine. Despite significantly higher concentrations of pollutants in the Ostrava region in all sampling periods, the levels of biomarkers were mostly comparable in both locations suggesting a possible role of adaptive response to environmental pollution in the Ostrava subjects. Whole genome expression analysis revealed significant differences between locations in expression profiles of genes participating in apoptosis, cell cycle regulation, DNA repair, inflammation and in metabolism of xenobiotics. Our results indicate that long-term exposure to high levels of environmental pollutants may lead to adaption of the organism to the effect of xenobiotics. However, the adaption leads to a shorter life-span of the affected population.
Supported by the Czech Ministry of the Environment (SP/1b3/8/08) and the Czech Ministry of Education (2B08005).
Pavel Rossner, Jr., Olena Beskid, Alena Milcova, Anna Pastorkova, Andrea Rossnerova, Jana Schmuczerova, Vlasta Svecova, Nana Tabashidze, Elena Tulupova, Jan Topinka, Radim J. Sram Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Videnska 1083, 142 20 Prague, Czech Republic .
-
-
-
Nanosilver Induced DNA Damage does not Correlate with Cell Survival
More LessAbstractAlthough silver and titanium dioxide nanoparticles (Ag NP and TiO2 NP) belong to the NP most often studied, the mechanisms of their biological effects are still not fully understood. Moreover, there are numerous discrepancies in the reports on the extent of DNA damage induced by Ag NP in various mammalian cells in in vitro studies. The available data on Ag NP genotoxicity in vitro are based on short-term assays, such as MTT or Neutral Red assay, and no attempt has been made to directly relate DNA damage to clonogenicity loss. Therefore, we undertook a detailed study of unfunctionalised Ag NP and TiO2 NP action on 3 mammalian cell lines: human hepatocellular liver carcinoma HepG2, human lung carcinoma A549 and human colorectal adenocarcinoma HT-29. The end-points examined in this report after 2h and 24h treatment with NP, were DNA breakage estimated by the comet assay and oxidative base damage recognized by formamido-pyrimidine glycosylase (FPG) and estimated with the FPG+comet assay. Further, the frequencies of histone γH2AX foci and micronuclei, apoptosis as well as metabolic activity (MTT assay) and clonogenic capacity were estimated. Each cell line had a different pattern of DNA breakage and base damage versus NP concentration and time of treatment. There were no increases in the frequencies of histone γH2AX foci and micronuclei as compared to those in the untreated cells. Our results provided no data that would link DNA damage induced by Ag NP to the early apoptosis or to the loss of clonogenic ability. Such a conclusion is especially convincing for 20 nm TiO2 NP which induce DNA damage at a level comparable to that of 20 nm Ag NP but, in contrast with 20 nm Ag NP, hardly affects clonogenic ability. This does not mean that DNA lesions induced by NP are harmless, especially at the organismal level. When incorrectly repaired, they may lead to mutations in proteins, in consequence bringing about various adverse effects on human health, including cancer predisposition, neurodegeneration, and immunodeficiency.
Sylwia Męczyńska-Wielgosz, Teresa Bartłomiejczyk, Iwona Grądzka, Anna Lankoff, Maria Wojewódzka, Grzegorz Wójciuk, Karolina Wójciuk, Maria Dusinska, Lucyna Kapka-Skrzypczak, Marcin Kruszewski
.
-
-
-
Means of Legal Protection of the Environment
More LessAbstractProtection of the environment, anywhere, requires carrying out three indispensable fundamental tasks to achieve the desired goal of raising the level of environmental awareness among the population; to avoid the risk of ignorance of the importance of preserving the environment, and to face excessive pollution cases. This is done by introducing the protection of the environment within educational programs in schools and universities; also using media and modern communications to prepare qualified professionals in the fields of environmental science to work at protecting the environment. This will safeguard against all kinds of pollution, by planning and implementation, so that the protection of the environment will be an element of the feasibility study of the projects to be set up, and the most important factor that controls human behavior in operational areas. Enactment of laws is necessary to protect the environment from attacks that can occur in any element, and the most effective laws are those that protect against pollution and prevent its occurrence; or even putting a deterrent in place such as penalties for the environmental violation. The aim of these sanctions is to limit the behaviors that causeenvironmental pollution by instilling a fear of punishment. Environmental protection laws have become one of the most important laws imposed over the last decade and this is a basic necessity for many countries to preserve the environment. Degrees of interest in environmental legislation and provisions contained therein, have varied as it progresses and develops. Developed countries with a high awareness but lacking in the development of legal rules, and underdeveloped countries differ in their positions on environmental laws, particularly concerning food shortage and poverty. However, legislations, for the most part, have been weak in terms of protection, or they did not implement them strongly enough. .
-