Metabolic inactivation of N-nitrosamines by cytochrome P-450 in vitro and in vivo.
Nitrite was formed on incubation of N-nitrosamines with both microsomal systems and a reconstituted system consisting of cytochrome P-450 and NADPH P-450 reductase from pig liver. Nitrite was not obtained when the nitrosamines were incubated with NADPH P-450 reductase alone or when molecular oxygen or NADPH was omitted. Various inhibitors of the microsomal monooxygenase decreased nitrite generation. Furthermore, nitrite and a substantially higher amount of nitrate could be found in the urine of rats given N-nitrosodiphenylamine. Diphenylamine was also detected. From in-vitro studies, it is concluded that denitrosation of N-nitrosamines is a cytochrome P-450-dependent process, which also occurs in vivo.
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004052:Diethylnitrosamine / Q000378:metabolism; D004159:Diphenylamine / Q000652:urine; D005260:Female; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000378:metabolism / Q000652:urine; D009602:Nitrosamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine
D002273:Carcinogens; D009566:Nitrates; D009573:Nitrites; D009602:Nitrosamines; C013161:N-nitroso(di-n-propyl)amine; D004052:Diethylnitrosamine; C002741:N-nitrosomorpholine; C012279:dibutylnitrosamine; D003577:Cytochrome P-450 Enzyme System; D004159:Diphenylamine; C023649:N-nitrosodiphenylamine