Multiplicity of induction patterns of rat liver microsomal mono-oxygenases and other polypeptides produced by administration of various xenobiotics.
Induction of hepatic microsomal mono-oxygenase species after administration of various xenobiotics is a well-documented phenomenon. To examine the number and specific species of rat liver microsomal membrane polypeptides involved in such responses, we have used sodium dodecyl sulphate/polyacrylamide-gel electrophoresis to analyse microsomal fractions from animals treated with a number of important xenobiotics. The following are the principal points to have emerged from this study. 1. A minimum of twelve electrophoretically distinct patterns of induction of haemopolypeptides and other polypeptides could be distinguished after administration, either singly or in certain combinations, of phenobarbital, 3-methylcholanthrene, polychlorinated biphenyls, 2-acetylaminofluorene, safrole (or isosafrole), pregnenolone-16 alpha-carbonitrile and ethanol. The patterns consisted of various permutations of the amounts of eight polypeptides of 47000-56000 mol.wt., of which at least three were haemopolypeptides. The possible identities of these polypeptides, which included species of cytochrome P-450, cytochrome P-448 and epoxide hydratase, are discussed. 2. Agents (3-methylcholanthrene, benzo[a]-pyrene, polychlorinated biphenyls, 2,3,7,8-tetrachlorodibenzo-p-dioxin and beta-naphthoflavone) that result in the induction of cytochrome P-448 caused a marked increase in two polypeptides of 54000 and 56000 mol.wt., whereas safrole and isosafrole induced only the former polypeptide. 3. Administration of 2-acetylaminofluorene resulted in the induction of two polypeptides; evidence is presented that suggests that one of these is a species of epoxide hydratase [cf. Levin, Lu, Thomas, Ryan, Kizer & Griffin (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 3240-3243] ANd that the other may be a novel haemopolypeptide. 4. The overall results emphasize the complexity of the responses exhibited by rat liver microsomal fractions to the administration of xenobiotics.
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010105:Oxygenases / Q000096:biosynthesis*; D010452:Peptide Biosynthesis; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D051381:Rats; D012451:Safrole / Q000494:pharmacology
D011285:Pregnenolone Carbonitrile; D000431:Ethanol; D008748:Methylcholanthrene; D015073:2-Acetylaminofluorene; D011078:Polychlorinated Biphenyls; D010105:Oxygenases; D012451:Safrole; D010634:Phenobarbital