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Arsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrow
WANG, A., A. D. KLIGERMAN, S. D. Holladay, D. C. WOLF, AND J. L. Robertson. Arsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrow. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS. John Wiley & Sons, Inc, Hoboken, NJ, 50(9):760-770, (2009).
This study was performed to see if a hypothesized mode of action of arsenicals, inhibition of DNA repair, would be detected in rat bladder transtiional cells, a site of arsenic induced cancer.
Arsenic is a recognized human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the urinary bladder (with cigarette smoking) and skin (with UV light exposure). Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include induction of DNA damage, inhibition of DNA damage repair, interference with cell cycle control, decreases in apoptosis, alteration in DNA methylation, and changes in bio-metabolism of other chemicals. We investigated the effects of arsenic in drinking water on DNA damage repair in urinary bladder transitional cells and on micronucleus formation in bone marrow. F344 rats were given 100 ppm arsenate [As(V)] or dimethylarsinic acid [DMA(V)] in drinking water for 1 week. The in vivo repair of a single oral gavage of cyclophosphamide-induced DNA damage, and the in vitro repair of in vitro hydrogen peroxide- or formaldehyde-induced DNA damage were measured by the Comet assay. DMA(V) did not affect cyclophosphamide-induced DNA damage induction or repair. Neither DMA(V) nor As(V) inhibited the in vitro repair of hydrogen peroxide- or formaldehyde-induced DNA damage, and neither increased the micronucleus frequency nor elevated the cyclophosphamide-increased micronucleus frequency. These results suggest arsenic carcinogenesis/cocarcinogenesis in the urinary bladder may not be via DNA damage repair inhibition. To our knowledge this is the first report of arsenic effects on DNA damage repair in the urinary bladder.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL CARCINOGENESIS DIVISION
CANCER BIOLOGY BRANCH