Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic.

Authors
Andrew-AS; Burgess-JL; Meza-MM; Demidenko-E; Waugh-MG; Hamilton-JW; Karagas-MR
Source
Environ Health Perspect 2006 Aug; 114(8):1193-1198
NIOSHTIC No.
20031231
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 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.
Keywords
Arsenic-compounds; Drinking-water; Exposure-levels; Exposure-assessment; Risk-factors; Risk-analysis; Lymphocytes; Epidemiology; Laboratory-testing; Cell-cultures; Models; Arsenites; Arsenates; Environmental-health
Contact
A.S. Andrew, Dartmouth Medical School, Section of Biostatistics and Epidemiology, 7927 Rubin 860, One Medical Center Dr., Lebanon, NH 03756 USA
CODEN
EVHPAZ
CAS No.
7440-38-2
Publication Date
20060801
Document Type
Journal Article
Email Address
Angeline.Andrew@dartmouth.edu
Funding Type
Grant
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T01-CCT-910446
Issue of Publication
8
ISSN
0091-6765
Source Name
Environmental Health Perspectives
State
AZ; NH
Performing Organization
University of Arizona, Tucson, Arizona
TOP