1887

Abstract

Abstract

The 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.

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/content/papers/10.5339/qproc.2012.mutagens.3.41
2012-03-01
2019-12-12
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http://instance.metastore.ingenta.com/content/papers/10.5339/qproc.2012.mutagens.3.41
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  • Received: 10 May 2012
  • Accepted: 10 May 2012
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