Correlation between Changes in Enzymatic Activities and Induction of Different Forms of Rat Liver Microsomal Cytochrome P‐450 after Phenobarbital‐, 3‐Methylcholanthrene‐ and 16α‐Cyanopregnenolone Treatment

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Abstract
Multiple forms of liver microsomal cytochrome P-450 in rats were identified on SDS[sodium dodecyl sulfate]-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 2 forms with apparent MW of 54,000 (RLvMc P-45054) and 50,000 (RLvMc P-45050) was obtained with phenobarbital, induction of RLvMc P-45055 and RLvMc P-45058 with 3-methylcholanthrene and induction of RLvMc P-45054 with 16.alpha.-cyanopregnenolone. The RLvMc P-45050 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-45055 and/or the RLvMc P-45058 was mainly associated with the formation of 2- and 3-hydroxybiphenyl and benzo(a)pyrene-7,8-dihydrodiol and RLvMc P-45054 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. 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.