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, Margaret R. Karagas

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

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 individual-level exposure data and biologic samples to investigate the effects of As exposure on a 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-acetoxyacetylaminofluorence (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 like to enhance the genotoxicity and mutagenicity of other directly genotoxic compounds, as part of a cocarcinogenic mechanism of action.

Original languageEnglish (US)
Pages (from-to)1193-1198
Number of pages6
JournalEnvironmental health perspectives
Volume114
Issue number8
DOIs
StatePublished - Aug 2006

Keywords

  • Arsenic
  • Arsenite
  • DNA repair
  • ERCC1
  • Molecular epidemiology
  • Nucleotide excision repair

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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