Induction of cytochrome P-450 isoenzymes in cultured monkey hepatocytes.
The effect of phenobarbital (PB), beta-naphthoflavone (beta-NF) and rifampicin (Rif) on the drug-metabolizing activity of cultured squirrel monkey hepatocytes was examined. The drug metabolizing activity (e.g. alkoxycoumarin dealkylase or steroid hydroxylase) gradually decreased during the culture period with 40-70% activity remaining at 72 hr. When 0.5 mM PB was added to the culture, the activities of 7-methoxycoumarin O-demethylase (MCOD) and 7-ethoxycoumarin O-deethylase (ECOD) increased to 6-7 fold higher level than those of control at 72 hr. Testosterone 6 beta-hydroxylase (6 beta-OH-T) and testosterone 16 beta-hydroxylase (16 beta-OH-T) activities were approx. 3-fold higher than those of the control. Addition of beta-NF significantly increased the activities of 7-ethoxyresorufin O-deethylase (EROD) and ECOD. Though statistically insignificant, Rif slightly increased 6 beta-OH-T activity. Western blot analysis indicated PB induced production of the CYP 2B and 3A subfamilies, while beta-NF and Rif induced that of the CYP 1A and the CYP 3A subfamily, respectively.
Nishibe
Y
Y
Shionogi Research Laboratory, Shionogi & Co. Ltd, Osaka, Japan.
Hirata
M
M
D015660:7-Alkoxycoumarin O-Dealkylase / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001571:Benzoflavones / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction; D007527:Isoenzymes / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010090:Oxidoreductases, O-Demethylating / Q000096:biosynthesis / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D012453:Saimiri; D013250:Steroid Hydroxylases / Q000096:biosynthesis / Q000378:metabolism; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D003374:Coumarins; D007527:Isoenzymes; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; C047335:7-methoxycoumarin-O-demethylase; D010090:Oxidoreductases, O-Demethylating; D013250:Steroid Hydroxylases; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases; C025619:steroid 16-beta-hydroxylase; D012293:Rifampin; D010634:Phenobarbital