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Arsenic Exposure Is Associated with Decreased DNA Repair In vitro and in Individuals Exposed to Drinking Water Arsenic
Angeline S. Andrew, Jefferey L. Burgess, Maria M. Meza, Eugene Demidenko, Mary G. Waugh, Joshua W. Hamilton and Margaret R. Karagas
Environmental Health Perspectives
Vol. 114, No. 8 (Aug., 2006), pp. 1193-1198
Published by: The National Institute of Environmental Health Sciences
Stable URL: http://www.jstor.org/stable/3655944
Page Count: 6
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The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individuallevel exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora (Mexico). Additionally, in corroborative laboratory studies, we examined the effects of As on DNA repair in a cultured human cell model. Arsenic exposure was associated with decreased expression of ERCC1 in isolated lymphocytes at the mRNA and protein levels. In addition, lymphocytes from As-exposed individuals showed higher levels of DNA damage, as measured by a comet assay, both at baseline and after a 2-acetoxyacetylaminofluorene (2-AAAF) challenge. In support of the in vivo data, As exposure decreased ERCC1 mRNA expression and enhanced levels of DNA damage after a 2-AAAF challenge in cell culture. These data provide further evidence to support the ability of As to inhibit the DNA repair machinery, which is likely to enhance the genotoxicity and mutagenicity of other directly genotoxic compounds, as part of a cocarcinogenic mechanism of action.
Environmental Health Perspectives © 2006 The National Institute of Environmental Health Sciences