title: Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water.
abstract: In West Bengal, India, more than 300,000 arsenic-exposed people are showing symptoms of arsenic toxicity, which include cancers of skin and different internal organs. Since only 15-20% of the exposed population manifest arsenic-induced skin lesions, it is thought that genetic variation might play an important role in arsenic toxicity and carcinogenicity. A total of 422 unrelated arsenic-exposed subjects (244 skin-symptomatic and 178 asymptomatic) were recruited for this study. Cytogenetic damage, as measured by chromosomal aberrations in lymphocytes and micronuclei formation in oral mucosa cells, urothelial cells and binucleated lymphocytes, was studied in unexposed, skin-symptomatic and asymptomatic individuals with similar socioeconomic status. Identification of null mutations in GSTT1 and GSTM1 genes were carried out by PCR amplification. GSTP1 SNPs, implicated in susceptibility to various cancers, were assessed by PCR-RFLP method. Symptomatic individuals had higher level of cytogenetic damage compared to asymptomatic individuals and asymptomatic individuals had significantly higher genotoxicity than unexposed individuals. No difference in allelic variants in GSTT1 and GSTP1 was observed between these 2 groups. Incidence of GSTM1 null gene frequencies was significantly higher in the asymptomatic group. Individuals with GSTM1-positive (at least one allele) had significantly higher risk of arsenic-induced skin lesions (odds ratio, 1.73; 95% confidence interval, 1.24-2.22). These results show a protective role of GSTM1 null in arsenic toxicity. This study also indicates that asymptomatic individuals are sub clinically affected and are also significantly susceptible to arsenic-induced genotoxicity.
authors.affiliation: Indian Institute of Chemical Biology, Kolkata, and West Bank Hospital, Howrah, India.
authors.forename: Pritha
authors.initials: P
authors.lastname: Ghosh
authors.forename: Anamika
authors.initials: A
authors.lastname: Basu
authors.forename: Julie
authors.initials: J
authors.lastname: Mahata
authors.forename: Sreemanti
authors.initials: S
authors.lastname: Basu
authors.forename: Mainak
authors.initials: M
authors.lastname: Sengupta
authors.forename: Jayanta K
authors.initials: JK
authors.lastname: Das
authors.forename: Angshuman
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Ajoy K
authors.initials: AK
authors.lastname: Sarkar
authors.forename: Lakshmikanta
authors.initials: L
authors.lastname: Mondal
authors.forename: Kunal
authors.initials: K
authors.lastname: Ray
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Giri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001151:Arsenic / Q000633:toxicity*; D004249:DNA Damage; D004781:Environmental Exposure; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced; D020641:Polymorphism, Single Nucleotide; D012871:Skin Diseases / Q000139:chemically induced / Q000235:genetics; D012923:Social Class; D014881:Water Supply
chemical_list: D001151:Arsenic; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human