Influence of ethanol and benzene on cytochrome P-450 fractions in rat liver microsomes.

The repartition and characteristics of liver microsomal cytochrome P-450 fractions from benzene- or ethanol-treated rats were compared to those observed either in untreated animals, or in rats treated by classic inducers, namely phenobarbital, 3-methylcholanthrene, or beta-naphthoflavone. DEAE-cellulose chromatography allowed the separation of four main cytochrome P-450 fractions called A (nonabsorbed), Ba, Bb, and Bc (successively eluted by a NaCl gradient). In control rats, and in ethanol- and benzene-treated animals, fractions A were predominant; phenobarbital, 3-methylcholanthrene, beta-naphthoflavone, and benzene induced Bb fractions. Enzymatic and immunological methods allowed a characterization of those cytochrome P-450 fractions. Fractions A are similar in all cases, and mainly active towards aniline. This aniline hydroxylase activity is especially increased by ethanol. As a rule, fractions Ba and Bc behave similarly and exhibit rather low monooxygenase activities. On the contrary, fractions Bb differ from each other as a function of the inducer. Phenobarbital-induced Bb fraction is different from all other Bb fractions and especially active towards benzphetamine. 3-Methylcholanthrene- and beta-naphthoflavone-induced Bb fractions are identical, but they are different from all other Bb fractions, and especially active towards 7-ethoxycoumarin. Fraction Bb induced by benzene is different from those induced by classic inducers, but may be identical to the Bb fraction of control animals. As a whole, benzene and ethanol appear to display inducing properties different from those of phenobarbital or polycyclic aromatic hydrocarbon-like inducers.