Comparison of the effects of various inducers on 7-alkoxycoumarin O-dealkylase activities in liver microsomes.

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The effects of six inducers and malotilate on 7-alkoxycoumarin 0-dealkylase activities in rat liver microsomes were examined. Phenobarbital (PB) (100 mg/kg) was administered intraperitoneally to rats for 6 days; 3-methylcholanthrene (3-MC) (40 mg/kg), β-naphthoflavone (β-NF) (40 mg/kg), isosafrole (150 mg/kg) and polychlorinated biphenyls (PCB) (100 mg/kg) were administered intraperitoneally for 3 days; isoniazid (INH) (50 mg/kg) was administered intraperitoneally for 10 days; and malotilate (500 mg/kg) was administered orally for 3 days. The 0-dealkylase activities toward 7-methoxycoumarin (7-MC), 7-ethoxycoumarin (7-EC) and 7-propoxycoumarin (7-PC) were examined 24 hr after the final administration of the drugs. The ratios of 7-EC 0-deethylase and 7-PC 0-depropylase to 7-MC 0-demethylase activity in the control and six inducer treated groups were compared. The ratios in the groups treated with the six compounds, each of which induces a different form(s) of cytochrome P-450 (P-450), were clearly different from each other. Therefore, the measurement of 7-alkoxycoumarin 0-dealkylase activities should be extremely useful for the routine determination of the molecular species of P-450. On the other hand, the ratio in the malotilate-treated group was different from that in any other inducer-treated group, so that there might be a possibility that malotilate induced a form(s) of P-450 that is different from any of the already known species.
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Comparison of the effects of various inducers on 7-alkoxycoumarin O-dealkylase activities in liver microsomes.

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