Effect of the length of alkyl chain on the cytochrome P450 dependent metabolism of N-diakylnitrosamines.
Liver microsomes from control and treated rats (P4501A, 2B, 2E1-induced) metabolize at variable metabolic rates eight N-nitroso-di-n-alkylamines, including five symmetrical (N-nitroso-dimethyl, -diethyl, -dipropyl, -dibutyl and -diamyl-amines) and four asymmetrical (N-nitrosomethylethyl, methylpropyl, methylbutyl, and methylamyl-amines), into aldehydes. Thus, the longer the alkyl chain of symmetrical N-nitrosamines, the smaller was the metabolic rate of the corresponding aldehyde formation. The chain length of the alkyl group of N-nitroso-methylalkylamines modified the oxidation of the alkyl moiety: the oxidation by CYP2E1 decreased as the n-alkyl chain length increased and conversely for the oxidation by CYP1A and CYP2B. Finally, the longer the n-alkyl chain length of asymmetrical N-nitrosamines, the greater was the oxidation of methyl groups.
Bellec
G
G
Laboratoire de Biochimie-Nutrition, Faculté de Médecine, Brest, France.
Goasduff
T
T
Dreano
Y
Y
Menez
J F
JF
Berthou
F
F
D000478:Alkylation; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D005557:Formaldehyde / Q000378:metabolism; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009602:Nitrosamines / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D002273:Carcinogens; D007527:Isoenzymes; D009602:Nitrosamines; D005557:Formaldehyde; D003577:Cytochrome P-450 Enzyme System