1887

Abstract

Abstract

In 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.

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/content/papers/10.5339/qproc.2012.mutagens.3.30
2012-03-01
2019-08-20
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http://instance.metastore.ingenta.com/content/papers/10.5339/qproc.2012.mutagens.3.30
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  • Received: 09 May 2012
  • Accepted: 09 May 2012
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