Document Detail


Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water.
MedLine Citation:
PMID:  16353154     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Pritha Ghosh; Anamika Basu; Julie Mahata; Sreemanti Basu; Mainak Sengupta; Jayanta K Das; Angshuman Mukherjee; Ajoy K Sarkar; Lakshmikanta Mondal; Kunal Ray; Ashok K Giri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  118     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-03-06     Completed Date:  2006-05-22     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2470-8     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2005 Wiley-Liss, Inc.
Affiliation:
Indian Institute of Chemical Biology, Kolkata, and West Bank Hospital, Howrah, India.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Arsenic / toxicity*
DNA Damage*
Environmental Exposure*
Female
Genetic Predisposition to Disease
Genetic Variation
Glutathione S-Transferase pi / genetics*
Glutathione Transferase / genetics*
Humans
India
Male
Middle Aged
Neoplasms / chemically induced
Polymorphism, Single Nucleotide
Skin Diseases / chemically induced,  genetics
Social Class
Water Supply*
Chemical
Reg. No./Substance:
7440-38-2/Arsenic; EC 2.5.1.-/glutathione S-transferase T1; EC 2.5.1.18/GSTP1 protein, human; EC 2.5.1.18/Glutathione S-Transferase pi; EC 2.5.1.18/Glutathione Transferase; EC 2.5.1.18/glutathione S-transferase M1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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