Activating and inactivating reactions controlling 2-naphthylamine mutagenicity.
Factors controlling 2-naphthylamine mutagenicity were studied using the Ames test. 1) Both rat liver microsomes and cytosolic proteins were required for generation of mutagenic metabolites. 2) 1-Hydroxy-2-naphthylamine, the major metabolite of 2-naphthylamine, was not mutagenic but cytotoxic to bacteria. 3) Ascorbic acid, reduced glutathione and conjugation reactions, such as glucuronidation, were strongly inhibiting 2-naphthylamine mutagenicity. 4) When isolated hepatocytes were used as the activating system mutagenic metabolites could not be detected. However cytotoxicity was detectable at doses of 2-naphthylamine greater than 0.2 mumol/10(6) cells. The results suggest that the formation of genotoxic metabolites of 2-naphthylamine is largely prevented in the intact, non-dividing rat hepatocyte.
D015081:2-Naphthylamine / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001711:Biotransformation; D005965:Glucuronates / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism*; D009281:Naphthalenes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D005965:Glucuronates; D009153:Mutagens; D009281:Naphthalenes; D015081:2-Naphthylamine; D005978:Glutathione; D001205:Ascorbic Acid