Carcinogenicity of dimethylarsinic acid (DMAV)

Samuel M. Cohen, Chris Le, Xiufen Lu, Marty Cano, Lora L. Arnold

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Dimethylarsinic acid (DMAV) administered at high doses in the diet or drinking water produces bladder tumors in rats, with females being more susceptible than males. In contrast, tumors are not produced when even higher doses are administered to mice, and in short-term studies (10 weeks) there are no toxic or preneoplastic changes in the urinary tract of hamsters. Cytotoxicity of the urothelium is induced within 6 h of administration, with consequent regenerative hyperplasia beginning after 3 days of administration. The toxicity and regeneration follows a dose response similar to the carcinogenic effects seen in a 2-year bioassay, and the hyperplasia is reversible after 10 weeks of administration. The two major urinary products of rats treated with DMAV are DMAV itself and trimethylarsine oxide (TMAO). However, micromolar concentrations of dimethylarsinous acid (DMAIII) are also produced. DMAIII is a highly cytotoxic organic trivalent metabolite of DMAV and other arsenicals, and is a possible proximate form of DMAV that produces the cytotoxicity of the urothelium. In vitro studies show comparable cytotoxicity of rat and human urothelial cell lines at micromolar concentrations for the trivalent arsenicals, but require millimolar concentrations of organic pentavalent arsenicals, such as DMAV and TMAO. Extrapolation of these findings in rodents to human risk must be made cautiously, because the doses used in these studies are several orders of magnitude greater than potential human exposures, and the metabolism of DMAV appears to differ significantly among species, especially in the rat.

Original languageEnglish (US)
Title of host publicationArsenic Exposure and Health Effects V
PublisherElsevier Inc.
Pages321-335
Number of pages15
ISBN (Electronic)9780080527567
ISBN (Print)9780444514417
DOIs
StatePublished - Dec 18 2003

Keywords

  • Cell proliferation
  • Cytotoxicity
  • Dimethylarsinic acid
  • Dimethylarsinous acid
  • Urinary bladder
  • Urinary metabolites

ASJC Scopus subject areas

  • Engineering(all)

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  • Cite this

    Cohen, S. M., Le, C., Lu, X., Cano, M., & Arnold, L. L. (2003). Carcinogenicity of dimethylarsinic acid (DMAV). In Arsenic Exposure and Health Effects V (pp. 321-335). Elsevier Inc.. https://doi.org/10.1016/B978-044451441-7/50025-7