Title: Arsenic Contamination in Ground water and Its Impact on Human Health: How Safe Are We?                                    

Abstract: More than 150 million individuals are exposed arsenic mainly through drinking water throughout the world.  In West Bengal, India over 26 million people are chronically exposed to arsenic through drinking water. Since 15 to 20% arsenic exposed individuals develop arsenic-induced skin lesions, it is assumed that genetic variation might play an important role for this arsenic susceptibility. An extensive study was carried out to assess the arsenic induced health effects and genetic damage in the skin lesions and no skin lesions individuals exposed to similar arsenic contaminated water. Different skin cancers observed in this population are the basal cell carcinoma, squamous cell carcinoma and in situ carcinoma i.e. Bowen’s diseases. Incidence of health effects was significantly high in skin lesions individuals compared to no skin lesions group. The genetic susceptibility studies were carried out through the study of single nucleotide polymorphisms (SNPs) in the GST group genes, p53, PNP, ERCC2 and XRCC3 as they might be involved arsenic metabolism and detoxification. p53 codon 72 Arg/Arg genotype, ERCC2 codon 751 Lys/Lys genotype, three SNPs of PNP and T241M polymorphism in XRCC3 were significantly high in the skin lesions group compared to that of the no skin lesions individuals. DNA repair deficiency study using Challenge assay proved strong evidence that the individuals with arsenic-induced skin lesions had suboptimal DNA repair capacity. In a two wave cross sectional epidemiological study, where same group of individuals were surveyed at two time points (2005-06 and 2010-11), we found decrease in water arsenic content helped to reduce only the genetic damage and dermatological disorders but the non-dermatological disorders were irreversible. Attempts have also been made to explore the epigenetic alterations that could lead to arsenic induced DNA damage and carcinogenic outcomes. We have found that arsenic induced epigenetic modulation leads to alteration in expression profile of key tumour suppressor genes like p16 and DAPK and DNA repair gene ERCC2.  In our arsenic mitigation program we have observed that rice has a significant contribution towards arsenic exposure when there is no arsenic in the drinking water and arsenic exposure through rice alone is sufficient to induce genetic damage in human.