Interaction of carbaryl and N-nitrosocarbaryl with microsomal monooxygenase activities.
The in vitro interactions of carbaryl and carcinogenic N-nitrosocarbaryl with rat liver microsomal monooxygenase activities are compared. The inhibitory effect of the nitroso-compound is demonstrated to be non-competitive on aminopyrine N-demethylase, p-nitroanisole O-demethylase and aniline hydroxylase. The nature of the inhibition induced by the parent amide is found to be competitive on aminopyrine N-demethylase and p-nitroanisole O-demethylase. Correspondingly, in vitro studies of the metabolism of the two compounds were carried out: they both yield formaldehyde. Moreover, N-nitrosocarbaryl is denitrosated through a NO-cytochrome P-450 complex during microsomal metabolism. The toxic effects and biological activities of the two compounds are discussed on the basis of data of metabolic studies and different patterns of enzyme inhibition.
Beraud
M
M
Groupe de Recherches sur la Toxicologie des Aliments et des Boissons, INSERM U87, Toulouse, France.
Forgue
M F
MF
Pipy
B
B
Derache
P
P
D000818:Animals; D012721:Carbaryl / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D003640:Dealkylation; D005260:Female; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
D009602:Nitrosamines; C008649:nitrosocarbaryl; D010105:Oxygenases; D012721:Carbaryl