Characterization of the cytochrome P-450 monooxygenase system of hamster liver microsomes. Effects of prior treatment with ethanol and other xenobiotics.
The cytochrome P-450 monooxygenase system of hamster liver microsomes and its response to prior treatment with ethanol and other xenobiotics have been examined. Male Syrian golden hamsters were administered ethanol (ETOH), phenobarbital (PB), 5,6-benzoflavone (BF) or isoniazid (INH). Each treatment resulted in a moderate increase (20-60%) in the specific content of liver microsomal cytochrome P-450 along with a unique hemeprotein ferrous carbonyl Soret maximum. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of liver microsomes revealed distinctive changes in protein banding patterns in the cytochrome P-450 (45-60 kDa) region with each treatment. NADPH: cytochrome c reductase activity was increased by both PB and INH, whereas cytochrome b5 content was increased by INH only. Microsomal oxidation of ETOH and aniline p-hydroxylation (expressed per nmol cytochrome P-450) were enhanced dramatically by ETOH and INH, whereas PB and BF had no effect on these enzymatic activities. Both ETOH and INH also increased zoxazolamine 6-hydroxylation but, in contrast to other rodent species, this drug-metabolizing activity was decreased in hamster liver microsomes after treatment with either PB or BF. Microsomal benzphetamine N-demethylation was decreased by ETOH, INH and BF administration and was only modestly enhanced after treatment with PB. ETOH and INH had no effect on the O-deethylation of 7-ethoxycoumarin, and enzymatic activity increased by BF but decreased by PB. These results demonstrate that the cytochrome P-450-dependent monooxygenase system of hamster liver microsomes responds to treatment with ETOH and other xenobiotics in a manner that is quantitatively and, in certain respects, qualitatively different from that reported for the rat, rabbit, and mouse.
Ardies
C M
CM
Alcohol Research and Treatment Center, Bronx Veterans Administration Medical Center, NY 10468.
Lasker
J M
JM
Lieber
C S
CS
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D001589:Benzphetamine / Q000378:metabolism; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000302:isolation & purification*; D010634:Phenobarbital / Q000494:pharmacology; D013045:Species Specificity; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D001589:Benzphetamine; D000431:Ethanol; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D007538:Isoniazid; D010634:Phenobarbital