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Decreased DNA repair gene expression among individuals exposed to arsenic in United States drinking water

  1. Angeline S. Andrew1,2,3,†,*,
  2. Margaret R. Karagas1,3,
  3. Joshua W. Hamilton2,3

Article first published online: 15 JAN 2003

DOI: 10.1002/ijc.10968

Issue

International Journal of Cancer

International Journal of Cancer

Volume 104, Issue 3, pages 263–268, 10 April 2003

Additional Information

How to Cite

Andrew, A. S., Karagas, M. R. and Hamilton, J. W. (2003), Decreased DNA repair gene expression among individuals exposed to arsenic in United States drinking water. International Journal of Cancer, 104: 263–268. doi: 10.1002/ijc.10968

Author Information

  1. 1

    Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH, USA

  2. 2

    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH, USA

  3. 3

    Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH, USA

  1. †

    Fax: +603-653-0578

*Dartmouth Medical School, 7927 Rubin 462M-3, One Medical Center Drive, Lebanon, NH 03756

Publication History

  1. Issue published online: 4 FEB 2003
  2. Article first published online: 15 JAN 2003
  3. Manuscript Accepted: 19 NOV 2002
  4. Manuscript Revised: 11 OCT 2002
  5. Manuscript Received: 3 JUN 2002

Funded by

  • NIEHS. Grant Number: ES07373
  • NCI. Grant Number: CA57494

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Keywords:

  • nucleotide excision repair;
  • ERCC1;
  • XPF;
  • XPG;
  • arsenic;
  • DNA repair;
  • molecular epidemiology;
  • lymphocytes

Abstract

Arsenic is well established as a human carcinogen, but its precise mechanism of action remains unknown. Arsenic does not directly damage DNA, but may act as a carcinogen through inhibition of DNA repair mechanisms, leading indirectly to increased mutations from other DNA damaging agents. The molecular mechanism underlying arsenic inhibition of nucleotide excision repair after UV irradiation (Hartwig et al., Carcinogenesis 1997;18:399–405) is unknown, but could be due to decreased expression of critical genes involved in nucleotide excision repair of damaged DNA. This hypothesis was tested by analyzing expression of repair genes and arsenic exposure in a subset of 16 individuals enrolled in a population based case-control study investigating arsenic exposure and cancer risk in New Hampshire. Toenail arsenic levels were inversely correlated with expression of critical members of the nucleotide excision repair complex, ERCC1 (r2 = 0.82, p < 0.0001), XPF (r2 = 0.56, p < 0.002), and XPB (r2 = 0.75, p < 0.0001). The internal dose marker, toenail arsenic level, was more strongly associated with changes in expression of these genes than drinking water arsenic concentration. Our findings, based on human exposure to arsenic in a US population, show an association between biomarkers of arsenic exposure and expression of DNA repair genes. Although our findings need verification in a larger study group, they are consistent with the hypothesis that inhibition of DNA repair capacity is a potential mechanism for the co-carcinogenic activity of arsenic. © 2003 Wiley-Liss, Inc.

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