Arsenic Exposure Is Associated with Decreased DNA Repair In Vitro and in Individuals Exposed to Drinking Water Arsenic

Details

• Personal Author:
  Andrew AS ; Burgess JL ; Demidenko E ; Hamilton JW ; Karagas MR ; Meza MM ; Waugh MG
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Arsenic Blood Cells, Cultured Drinking Water Environmental Health Environmental Monitoring Epidemiology Inorganic Chemicals Laboratories Occupational Health Risk Assessment Risk Factors Safety

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• Keywords:
  Arsenates Arsenic-compounds Arsenites Cell-cultures Drinking-water Environmental-health Exposure-assessment Exposure-levels Laboratory-testing Lymphocytes Models Risk-analysis Risk-factors

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• ISSN:
  0091-6765
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Arizona ; New Hampshire ; OSHA Region 1 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  114
• Issue:
  8
• NIOSHTIC Number:
  nn:20031231
• Citation:
  Environ Health Perspect 2006 Aug; 114(8):1193-1198
• Contact Point Address:
  A.S. Andrew, Dartmouth Medical School, Section of Biostatistics and Epidemiology, 7927 Rubin 860, One Medical Center Dr., Lebanon, NH 03756 USA
• Email:
  Angeline.Andrew@dartmouth.edu
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Federal Fiscal Year:
  2006
• Performing Organization:
  University of Arizona, Tucson, Arizona
• Peer Reviewed:
  True
• Start Date:
  19950701
• Source Full Name:
  Environmental Health Perspectives
• End Date:
  20060630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:bdb8c769053718bd10149073c5636742f7afc2899f725fc496d0733f7cc52bb7d6cd31d4971a36c3bc248d82e71cd0540c2cdb08dcf37b2089ffa75a5b8b3c45
• Download URL:
  https://stacks.cdc.gov/view/cdc/191541/cdc_191541_DS1.pdf
• File Type:
  [PDF - 141.46 KB ]