Differential effects of cytochrome P450-inducers on promutagen activation capabilities and enzymatic activities of S-9 from rat liver.

Studies have been conducted to determine aryl hydrocarbon hydroxylase, benzphetamine-N-demethylase, epoxide hydrase and glutathione S-transferase activities and cytochrome P-450 content in the liver 9000xg supernatant fractions from rats treated with either phenobarbital, beta-naphthoflavone, ARoclor 1254 or a combination of phenobarbital and beta-naphthoflavone. The metabolic activation of 2-anthramine, 2-acetylaminofluorene, 3-methylcholanthrene, and benzo(a)pyrene to metabolites that are mutagenic in Salmonella typhimurium TA1535 or TA98 by S-9 from rats treated with these inducers was also determined. The induction of drug metabolizing enzymes in the S-9 from Aroclor or phenobarbital plus beta-naphthoflavone treated animals was very similar. The overall results seem to indicate that a combination treatment of phenobarbital and beta-naphthoflavone can be used as a substitute for Aroclor 1254 as inducer for enzyme activity and for the in vitro activation of promutagens to mutagenic metabolites in Salmonella mutagenesis assay systems.