title: Arsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrow.
abstract: Arsenic is a human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the skin and urinary bladder. Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include oxidative stress induction and inhibition of DNA damage repair. 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 cyclophosphamide (CP)-induced DNA damage resulting from a single oral gavage of CP, and the in vitro repair of hydrogen peroxide (H(2)O(2))- or formaldehyde-induced DNA damage, resulting from adding H(2)O(2) or formaldehyde into cell medium, were measured by the Comet assay. DMA(V) effects were not observed on either CP-induced DNA damage induction or on DNA repair. Neither DMA(V) nor As(V) increased the H(2)O(2)- or formaldehyde-induced DNA damage, and neither inhibited the repair of H(2)O(2)-induced DNA damage. Neither DMA(V) nor As(V) increased the micronucleus frequency, nor did they elevate micronucleus frequency resulting from CP treatment above the level observed by the treatment with CP alone. These results suggest that 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.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Blacksburg, Virginia 24061, USA. amywang@vt.edu
authors.forename: Amy
authors.initials: A
authors.lastname: Wang
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kligerman
authors.forename: Steven D
authors.initials: SD
authors.lastname: Holladay
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wolf
authors.forename: John L
authors.initials: JL
authors.lastname: Robertson
mesh_terms: D000818:Animals; D001149:Arsenates / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects*; D002101:Cacodylic Acid / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D005557:Formaldehyde / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000633:toxicity; D015162:Micronucleus Tests; D051381:Rats; D011916:Rats, Inbred F344; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014881:Water Supply
chemical_list: D001149:Arsenates; D005557:Formaldehyde; D002101:Cacodylic Acid; D006861:Hydrogen Peroxide; C025657:arsenic acid