Increase by deoxycholic acid of the colonic nuclear damage induced by known carcinogens in C57BL/6J mice

J Natl Cancer Inst. 1986 Jun;76(6):1129-32.

Abstract

Intrarectal exposure of the colon epithelium of the C57BL/6J female mouse to deoxycholic acid [(DCA) CAS: 83-44-3] markedly increased its sensitivity to orally administered 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8]. While 4 mg DMH/kg body weight by itself increased the level of nuclear damage from a background level of 0.2-0.45 aberration per crypt, DMH when combined with DCA at a dose of 150 mg/kg increased the aberrations from 0.2 to 1.75 per crypt. This effect was observed over a wide range of DCA doses (20-300 mg/kg) and was evident when DMH was given up to 10 hours after the DCA. Similar results were observed with DCA in conjunction with benzo[a]pyrene (CAS: 50-32-8) and 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (CAS: 77094-11-2), though in these cases the time at which the peak of nuclear aberrations occurred was somewhat later. No enhancement was seen with DCA and gamma-radiation. These results show that DCA can enhance the nucleotoxic effects of several carcinogens and suggest that DCA can act as a cocarcinogen. The enhancement may be due to the effect of the bile acid on proliferation of the colon epithelial cells or to its effect on the permeability of mucosal cells.

MeSH terms

  • 1,2-Dimethylhydrazine
  • Animals
  • Carcinogens*
  • Cell Nucleus / drug effects*
  • Cocarcinogenesis
  • Colon / drug effects*
  • Colonic Neoplasms / chemically induced
  • Deoxycholic Acid
  • Dimethylhydrazines
  • Dose-Response Relationship, Drug
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Mitotic Index / drug effects
  • Time Factors

Substances

  • Carcinogens
  • Dimethylhydrazines
  • Deoxycholic Acid
  • 1,2-Dimethylhydrazine