Nuclear aberrations as a short-term test for genotoxicity to the colon: evaluation of nineteen agents in mice.
The genotoxicity of 16 agents including several hydrazines, nitrosamines, aromatic amines, polycyclic hydrocarbons, and other related compounds and three known inhibitors of carcinogenesis was assessed in the murine colonic nuclear aberration assay. Of the seven agents considered positive for colonic DNA damage, five were large bowel carcinogens. All structural analogues of the intestinal carcinogens that are tumorigenic for other organs, with the exception of benzo[a]pyrene, were negative in the colonic nuclear aberration assay as were all noncarcinogens tested. The metabolic inhibitor disulfiram completely inhibited 1,2-dimethylhydrazine-induced colonic nuclear damage, while inhibition was less marked for the antioxidants butylated hydroxyanisole and caffeic acid. The versatility of the assay as an indicator of colonic genotoxicity resulting from carcinogen exposure is discussed.
D019813:1,2-Dimethylhydrazine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity*; D002869:Chromosome Aberrations; D003106:Colon / Q000187:drug effects* / Q000648:ultrastructure; D004127:Dimethylhydrazines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004221:Disulfiram / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D008297:Male; D008763:Methylhydrazines / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D009152:Mutagenicity Tests / Q000379:methods*
D000975:Antioxidants; D002273:Carcinogens; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D019813:1,2-Dimethylhydrazine; D004221:Disulfiram