Increase by deoxycholic acid of the colonic nuclear damage induced by known carcinogens in C57BL/6J mice.
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.
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D019813:1,2-Dimethylhydrazine; D000818:Animals; D002273:Carcinogens; D002467:Cell Nucleus / Q000187:drug effects*; D003043:Cocarcinogenesis; D003106:Colon / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000139:chemically induced; D003840:Deoxycholic Acid; D004127:Dimethylhydrazines; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008940:Mitotic Index / Q000187:drug effects; D013997:Time Factors
D002273:Carcinogens; D004127:Dimethylhydrazines; D003840:Deoxycholic Acid; D019813:1,2-Dimethylhydrazine