arsenic biotransformation as a cancer promoting factor by inducing dna damage and disruption of repair mechanisms砷的生物转化为癌症促进因子诱导的dna损伤和破坏的修复机制.pdfVIP

SAGE-Hindawi Access to Research Molecular Biology International Volume 2011, Article ID 718974, 11 pages doi:10.4061/2011/718974 Review Article Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms Victor D. Martinez,1, 2 Emily A. Vucic,1 Marta Adonis,2 Lionel Gil,2 and Wan L. Lam1 1 Department of Integrative Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC, Canada V5Z 1L3 2 Biomedical Sciences Institute, Faculty of Medicine, University of Chile, Independencia 1027, 8380453 Santiago, Chile Correspondence should be addressed to Victor D. Martinez, vmartinez@bccrc.ca Received 16 March 2011; Accepted 6 June 2011 ´ ´ Academic Editor: Frederic Coin Copyright © 2011 Victor D. Martinez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells