NICOTINE AND SOME CARCINOGENS IN SPECIAL REFERENCE TO THE HEPATIC DRUG-METABOLIZING ENZYMES

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Abstract
When rats were fed 2-acetylaminofluorene (AAF) containing diet (0.029%), AAF hydraxylaae activity in the liver microsomes was enhanced with maximum increase (80%) at 3 wk. after the feeding. Pretreatment with 20 mg/kg of 3-methylcholanthrene (MC) caused an maximum increase (55%) 24 hr. after the injection. Pretreatment with AAF (for 3 wk.), MC (20 mg/kg, before 24 hr.) and 3,4-benzpyrene (BP) (20 mg/kg, before 24 hr.) enhanced nicotine metabolizing activity in rat liver microsomes with about 50%, 100%, and 80% increases, respectively. Pretreatment with nicotine also caused an increase in AAF hydroxylase activity with maximum elevation at 24 hr. after the injection and in doses of 40 mg/kg. When nicotine (40 mg/kg), cotinine (20 mg/kg), ntkethamide (40 mg/kg) and MC (25 mg/kg) were pre-administered to rats, AAF hydroxylase was enhanced about 130%, 50%, 155%, and 260% after 24 hr., respectively. Pretreatments with nicotine (40 mg/kg), cotinine (40 mg/kg), BP (20 mg/kg) and MC (25 mg/kg) enhanced BP hydroxylase about 90%, 100%, 120%, and 180% after 24 hr., respectively. The increased AAF and BP hydroxylase activities by nicotine, cotinine and MC were inhibited by ethlonine.