Correlation between changes in enzymatic activities and induction of different forms of rat liver microsomal cytochrome P-450 after phenobarbital-, 3-methylcholanthrene- and 16 alpha-cyanopregnenolone treatment.
Multiple forms of liver microsomal cytochrome P-450 in rats were identified on SDS-polyacrylamide gels stained for protein and peroxidase activity after induction with phenobarbital, 3-methylcholanthrene, and 16 alpha-cyanopregnenolone. The induced forms were correlated to the in vitro metabolism of biphenyl, benzo(a)pyrene and the steroids 4-androstene-3,17-dione and 5 alpha-androstane-3 alpha,17 beta-diol. Induction of two forms with apparent molecular weights of 54,000 (RLvMc P-450 54) AND 50,000 (RLvMc P-450 50) was obtained with phenobarbital, induction of RLvMc P-450 55 and RLvMc P-450 58 with 3-methylcholanthrene and induction of FLvMc P-450 54 with 16 alpha-cyanopregnenolone. The RLvMc P-450 50 was mainly associated with the formation of benzo(a)pyrene-4,5-dihydrodiol, and 7 alpha-hydroxy-4-androstene-3,17-dione. The RLvMc P-450 55 and/or the RLvMc P-450 58 was mainly associated with the formation of 2- and 3-hydroxybiphenyl and benzo(a)pyrene-7,8-dihydrodiol and FLvMc P-450 54 was to some extent associated with the formation of benzo(a)pyrene-4,5-dihydrodiol and several metabolites of 5 alpha-androstane-3 alpha, 17 beta-diol. It is suggested that SDS-polyacrylamide gel electrophoresis may be a valuable complement to enzyme assays in evaluating effects of drugs and environmental chemicals on the liver microsomal hydroxylase system.
D015113:Androstane-3,17-diol / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism; D001713:Biphenyl Compounds / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology*; D008970:Molecular Weight; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology*; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats
D001580:Benzopyrenes; D001713:Biphenyl Compounds; D015113:Androstane-3,17-diol; D000735:Androstenedione; D008748:Methylcholanthrene; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital