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

R. Toftgård, O. G. Nilsen, M. Ingelman‐Sundberg, Jan-Ake Gustafsson

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43 Scopus citations

Abstract

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 16α-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 5α-androstane-3α,17β-diol. Induction of two forms with apparent molecular weights 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 16α-cyanopregnenolone. The RLvMc P-45050 was mainly associated with the formation of benzo(a)pyrene-4,5-dihydrodiol, and 7α-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 5α-androstane-3α,17β-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.

Original languageEnglish (US)
Pages (from-to)353-361
Number of pages9
JournalActa Pharmacologica et Toxicologica
Volume46
Issue number5
DOIs
StatePublished - Jan 1 1980

Keywords

  • Cytochrome P‐450‐induction
  • liver microsomal metabolism
  • rat

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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