Inhibition of two rat hepatic microsomal drug-metabolizing enzymes by a carcinogenic N-nitrosated pesticide: N-nitrosocarbaryl.
N-Nitrosocarbaryl (N-methyl-1-naphthyl N-nitrosocarbamate) was intraperitoneally administered to male and female rats on four consecutive days at the following doses: 6.25 mg, 12.5 mg, 25 mg and 50 mg/kg body weight/day in olive oil solution; the controls received just the oil. In a second experiment, a daily intraperitoneal dose of 25 mg/kg of N-nitrosocarbaryl was given for 1, 2, 3 or 4 days; the animals were killed 24 h after the last treatment. The two following microsomal enzymatic activities were assayed: aniline aromatic hydroxylase and p-nitroanisole O-demethylase; the levels of cytochrome P-450, proteins and RNA were measured in the hepatic microsomal fraction. N-Nitrosocarbaryl is an inhibitor of the two investigated microsomal monooxygenases at doses of 25 and 50 mg/kg when administered on 4 consecutive days. During the daily administration, enzyme inhibition is seen in females after one day of treatment whereas cytochrome P-450 only becomes lowered after 4 days of administration. In males, no modification of this parameter is observed whereas the activities of microsomal monooxygenases are inhibited. These results suggest that N-nitrosocarbaryl could act on the active sites of the enzymes which metabolize aniline and p-nitroanisole.
D000815:Aniline Hydroxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001835:Body Weight / Q000187:drug effects; D012721:Carbaryl / Q000031:analogs & derivatives* / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009575:Nitroanisole O-Demethylase / Q000037:antagonists & inhibitors*; D009602:Nitrosamines / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats
D009602:Nitrosamines; D011506:Proteins; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; C008649:nitrosocarbaryl; D009575:Nitroanisole O-Demethylase; D010088:Oxidoreductases; D000815:Aniline Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D012721:Carbaryl