Oxidative and conjugative metabolism of xenobiotics by isolated rat and hamster acinar cells.
Isolated rat and hamster acinar cell suspensions possess the ability to carry out the cytochrome P-450-dependent O-deethylation of 7-ethoxycoumarin, 2-,3-, and 4-hydroxylation of biphenyl and 3-hydroxylation of benzo(a)pyrene. Rat and hamster acinar cells isolated from 5,6-benzoflavone-pretreated animals oxidize all three substrates at measurable rates. These rates are considerably lower (16-210-fold in the rat and 290-2670-fold in the hamster) than those in incubations using hepatocytes isolated from 5,6-benzoflavone-pretreated animals. Hydroxylation of biphenyl at the 2-, 3-, and 4-positions proceeds at similar rates in rat acinar cells. The rate of 3-hydroxybiphenyl formation is barely detectable in hamster acinar cells where the rates of 2- and 4-hydroxybiphenyl formation are slower than in the rat. No detectable oxidation products of 7-ethoxycoumarin, biphenyl, or benzo(a)pyrene are found with acinar cells of either species isolated from untreated and phenobarbital-pretreated animals. The O-deethylation of 7-ethoxycoumarin in rat and hamster acinar cells is decreased in the presence of inhibitors of the cytochrome P-450-dependent monooxygenase system, 7,8-benzoflavone being much more effective than metyrapone. The deethylation product of 7-ethoxycoumarin, 7-hydroxycoumarin, is conjugated with sulfate and glucuronic acid moieties at appreciable rates by acinar cells isolated from both rat and hamster. Pretreatment of rats and hamsters with either 5,6-benzoflavone or phenobarbital has little effect on the rates of conjugation in isolated acinar cell preparations.
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D001571:Benzoflavones / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000378:metabolism; D003374:Coumarins / Q000378:metabolism; D006224:Cricetinae; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D010084:Oxidation-Reduction; D010179:Pancreas / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013045:Species Specificity; D019324:beta-Naphthoflavone
D001564:Benzo(a)pyrene; D001571:Benzoflavones; D001713:Biphenyl Compounds; D003374:Coumarins; D004364:Pharmaceutical Preparations; D019324:beta-Naphthoflavone; C010574:biphenyl; C017299:7-ethoxycoumarin