Mutagenicity of five arylamines after metabolic activation with isolated dog and human hepatocytes.
The mutagenicity of benzidine (BZ) N-acetylbenzidine (MABZ), N,N'-diacetylbenzidine (DABZ), 4-aminobiphenyl (4-AB) and 2-aminoanthracene (2-AA) towards Salmonella typhimurium strain TA1538 was measured in the presence of isolated hepatocytes from dog and man. The influence of paraoxon, an inhibitor of the deacetylation reaction, on the mutagenicity of these compounds was also investigated. Obvious interspecies differences in the mutagenic activation of benzidine and its acetylated-derivatives were seen. However, with liver cell preparations from both species it was found that MABZ and DABZ were more mutagenic than BZ itself. 4-AB appeared to be weakly mutagenic in the presence of human hepatocytes but non-mutagenic with dog hepatocytes. 2-AA was highly mutagenic in both species. When human hepatocytes were used as the metabolic factor, the mutagenicity of all arylamines decreased in the presence of paraoxon. With dog hepatocytes, however, the mutagenicity of all arylamines except DABZ was enhanced in the presence of paraoxon.
D000328:Adult; D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes / Q000378:metabolism*; D001560:Benzidines / Q000378:metabolism*; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004285:Dogs; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D010261:Paraoxon / Q000494:pharmacology; D013045:Species Specificity
D000611:Aminobiphenyl Compounds; D000873:Anthracenes; D001560:Benzidines; D002273:Carcinogens; D009153:Mutagens; C006757:4-biphenylamine; C006593:2-anthramine; D003577:Cytochrome P-450 Enzyme System; D010261:Paraoxon