Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water

Ghosh, Pritha and Basu, Anamika and Mahata, Julie and Basu, Sreemanti and Sengupta, Mainak and Das, Jayanta K and Mukherjee, Angshuman and Sarkar, Ajoy K and Mondal, Lakshmikanta and Ray, Kunal and Giri, Ashok K (2006) Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water. Int. J. Cancer, 118 (10). pp. 2470-2478.

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    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 mto 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 mwas 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 arsenicinduced genotoxicity.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/471
    Subjects: Molecular & Human Genetics
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Mr Shyamal Nath
    Date Deposited: 02 Nov 2011 14:01
    Last Modified: 03 Feb 2012 11:51
    Official URL: htpp://dx.doi.org/10.1002/ijc.21640
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