A comparative study of the effects of benzene, toluene, and xylenes on their in vitro metabolism and drug-metabolizing enzymes in rat liver.

Male Sprague-Dawley rats were injected ip with benzene, toluene, or a mixture of xylene isomers at 20 mmol hydrocarbon/kg daily for 3 days. The effects of administration of these hydrocarbons upon their own in vitro metabolism, as well as upon cytochrome P-450, NADPH-cytochrome c reductase, aminopyrine N-demethylase, aniline hydroxylase, glutathione, glutathione S-transferase, and UDPglucuronyltransferase in liver were studied. Each hydrocarbon studied increased its own in vitro metabolism. Benzene had no effect on the metabolism of toluene or xylenes. Toluene and xylenes increased the metabolism of benzene, toluene, and xylenes. Cytochrome P-450 was elevated by toluene and xylenes, but was not affected by benzene. NADPH-cytochrome c reductase was induced by all three hydrocarbons. Aminopyrine N-demethylase and aniline hydroxylase were induced by toluene and xylenes and were not affected by benzene. Glutathione was elevated by benzene, decreased by xylenes, and not affected by toluene. Glutathione S-transferase was induced differentially by these hydrocarbons toward various substrates: toward 1-chloro-2,4-dinitrobenzene by benzene and toluene, toward 1,2-dichloro-4-nitrobenzene by benzene and xylenes, and no effect toward 1,2-epoxy-3-(p-nitrophenoxy)propane by any hydrocarbons. UDPglucuronyltransferase was induced by benzene and toluene when o-aminophenol and phenol were used as the substrate. Xylenes had no effect. Benzene was more effective at inducing conjugation enzymes. Xylenes were more effective at inducing cytochrome P-450 dependent enzymes. Toluene was equipotent at inducing both types of enzymes. The results indicate that the addition of methyl groups to the aromatic ring affects the inductive pattern of these monocyclic aromatic hydrocarbons.