TY - JOUR
T1 - 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
AU - Toftgård, R.
AU - Nilsen, O. G.
AU - Ingelman‐Sundberg, M.
AU - Gustafsson, Jan-Ake
PY - 1980/1/1
Y1 - 1980/1/1
N2 - 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.
AB - 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.
KW - Cytochrome P‐450‐induction
KW - liver microsomal metabolism
KW - rat
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U2 - 10.1111/j.1600-0773.1980.tb02466.x
DO - 10.1111/j.1600-0773.1980.tb02466.x
M3 - Article
C2 - 7376887
AN - SCOPUS:0018824731
VL - 46
SP - 353
EP - 361
JO - Acta Pharmacologica et Toxicologica
JF - Acta Pharmacologica et Toxicologica
SN - 0001-6683
IS - 5
ER -