This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 0192623309334147v1 37/4/425    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Wang, A. Articles by Robertson, J. L. PubMed PubMed Citation Articles by Wang, A. Articles by Robertson, J. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ARSENIC COMPOUNDS DIMETHYLARSENIC ACID Social Bookmarking                         What's this?

Dimethylarsinic Acid in Drinking Water Changed the Morphology of Urinary Bladder but Not the Expression of DNA Repair Genes of Bladder Transitional Epithelium in F344 Rats

¹ Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
² Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency (EPA), Research Triangle Park, North Carolina, USA
³ National Center for Environmental Assessment, US EPA, Research Triangle Park, North Carolina, USA

Correspondence: Amy Wang, National Center for Environmental Assessment (B-243-01), Office of Research and Development, US EPA, Research Triangle Park, NC 27711, USA; e-mail:amywang{at}vt.edu.

Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In F344 rats, dimethylarsinic acid (DMA[V]) increases transitional cell carcinoma. Arsenic-induced inhibition of DNA repair has been reported in cultured cell lines and in lymphocytes of arsenic-exposed humans, but it has not been studied in urinary bladder. Should inhibition of DNA damage repair in transitional epithelium occur, it may contribute to carcinogenesis or cocarcinogenesis. We investigated morphology and expression of DNA repair genes in F344 rat transitional cells following up to 100 ppm DMA(V) in drinking water for four weeks. Mitochondria were very sensitive to DMA(V), and swollen mitochondria appeared to be the main source of vacuoles in the transitional epithelium. Real-time reverse transcriptase polymerase chain reaction (Real-Time RT PCR) showed the mRNA levels of tested DNA repair genes, ataxia telangectasia mutant (ATM), X-ray repair cross-complementing group 1 (XRCC1), excision repair cross-complementing group 3/xeroderma pigmentosum B (ERCC3/XPB), and DNA polymerase β (Polβ), were not altered by DMA(V). These data suggested that either DMA(V) does not affect DNA repair in the bladder or DMA(V) affects DNA repair without affecting baseline mRNA levels of repair genes. The possibility remains that DMA(V) may lower damage-induced increases in repair gene expression or cause post-translational modification of repair enzymes.

Key Words: arsenic • dimethylarsinic acid • urothelium • DNA damage repair • ultrastructure

This version was published on June 1, 2009

Toxicologic Pathology, Vol. 37, No. 4, 425-437 (2009)
DOI: 10.1177/0192623309334147


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?