Studies on the mutagenic activation of heterocyclic amines by cynomolgus monkey, rat and human microsomes show that cynomolgus monkeys have a low capacity to N-oxidize the quinoxaline-type heterocyclic amines.
A number of mutagens and carcinogens have been isolated from cooked meats. In the current study we investigated the ability of hepatic microsomes from cynomolgus monkeys, Fischer-344 rats and humans to metabolically activate these compounds. Monkeys had almost no capacity to activate the quinoxaline-type compounds to mutagens in the Ames test relative to rats and humans but were able to activate the quinoline, pyridoindole and pyridoimidazole compounds. Differences in the mutagenicity of the quinoline and quinoxaline compounds by monkeys and rats was related to differences in cytochrome P-450-mediated N-oxidation between the species. This suggests that monkeys and rats may have different hepatic cytochrome P-450 isozymes, which are important for the metabolic activation of quinolines and quinoxalines, or that the orthologous monkey cytochromes show a select substrate specificity for the quinolines over the quinoxalines.
Davis
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CD
Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-0037.
Adamson
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RH
Snyderwine
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EG
D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics / Q000633:toxicity; D007211:Indoles / Q000493:pharmacokinetics*; D008252:Macaca fascicularis; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D011804:Quinolines / Q000493:pharmacokinetics*; D011810:Quinoxalines / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D007093:Imidazoles; D007211:Indoles; D009153:Mutagens; D011804:Quinolines; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D003577:Cytochrome P-450 Enzyme System