EFFECT OF THE LENGTH OF ALKYL CHAIN ON THE CYTOCHROME-P450 DEPENDENT METABOLISM OF N-DIALKYLNITROSAMINES

Liver microsomes from control and treated rats (P4501A, 2B, 2E1-induce d) metabolize at variable metabolic rates eight N-nitroso-di-n-alkylam ines, including five symmetrical (N-nitroso-dimethyl, -diethyl, -dipro pyl, -dibutyl and -diamyl amines) and four asymmetrical (N-nitroso-met hylethyl, methylpropyl, methylbutyl, and methylamyl-amines), into alde hydes. Thus, the longer the alkyl chain of symmetrical N-nitrosamines, the smaller was the metabolic rate of the corresponding aldehyde form ation. The chain length of the alkyl group of N-nitroso-methylalkylami nes modified the oxidation of the alkyl moiety; the oxidation by CYP2E 1 decreased as the n-alkyl chain length increased and conversely for t he oxidation by CYP1A and CYP2B. Finally, the longer the n-alkyl chain of asymmetrical N-nitrosamines, the greater was the oxidation of meth yl groups.