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 bact...

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Bibliographic Details
Published in:Archives of toxicology 1982-09, Vol.50 (3-4), p.259-266
Main Authors: Bock-Hennig, B S, Ullrich, D, Bock, K W
Format: Article
Language:English
Subjects:
2-Naphthylamine - metabolism
2-Naphthylamine - toxicity
Animals
Ascorbic Acid - pharmacology
Biotransformation
Glucuronates - metabolism
Glutathione - pharmacology
In Vitro Techniques
Inactivation, Metabolic
Liver - drug effects
Liver - metabolism
Mutagens - metabolism
Naphthalenes - metabolism
Rats
Rats, Inbred Strains
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Summary: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.
ISSN:0340-5761
1432-0738
DOI:10.1007/BF00310858