Promotion of NCI-Black-Reiter male rat bladder carcinogenesis by dimethylarsinic acid an organic arsenic compound

Cancer Lett. 1998 Dec 11;134(1):29-36. doi: 10.1016/s0304-3835(98)00237-7.


Dimethylarsinic acid (DMAA) is a major metabolite of inorganic arsenicals in mammals. In the present study, we investigated its promoting effects on urinary bladder carcinogenesis in NCI-Black-Reiter (NBR) rats, which lack alpha2u-globulin synthesizing ability. Male 9-14-week-old NBR rats were treated sequentially with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for 4 weeks and then given 100 ppm DMAA in their drinking water (group 1) for 32 weeks. Induction of preneoplastic lesions (papillary or nodular hyperplasia) in this DMAA-treated group was significantly increased as compared to the carcinogen alone control group (P < 0.01). The development of carcinomas was also enhanced and a significant increase in the 5-bromo-2'-deoxyuridine (BrdU) labeling index of the urinary bladder epithelial cells was observed for the DMAA treatment group. These results indicate that DMAA has promoting effects on urinary bladder carcinogenesis even in NBR rats, so its effects are not dependent on the presence of alpha2u-globulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpha-Globulins / analysis
  • Animals
  • Butylhydroxybutylnitrosamine
  • Cacodylic Acid / adverse effects*
  • Cacodylic Acid / urine
  • Carcinogenicity Tests
  • DNA, Neoplasm / biosynthesis
  • DNA, Neoplasm / drug effects
  • Herbicides / adverse effects*
  • Hyperplasia / chemically induced
  • Immunohistochemistry
  • Kidney / chemistry
  • Kidney / cytology
  • Male
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / pathology
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Strains
  • Urinary Bladder / drug effects
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / chemically induced*
  • Urinary Bladder Neoplasms / pathology


  • Alpha-Globulins
  • DNA, Neoplasm
  • Herbicides
  • alpha 2u globulin
  • Butylhydroxybutylnitrosamine
  • Cacodylic Acid