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.
D000818:Animals; D001554:Benzene / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology; D002848:Chromatography, DEAE-Cellulose; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005779:Immunodiffusion / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D000431:Ethanol; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D001554:Benzene; D010634:Phenobarbital