Hydroxylation of carbon atoms of the alkyl chain of symmetrical N-nitrosodialkylamines by rat liver microsomes

Liver microsomal preparations from control and treated rats (cytochromes P450 1A, 2B, 3A and 2E1-induced) metabolized at variable metabolic rates three nitrosodialkylamines (N-nitroso-dipropyl, dibutyl and diamyl-amines) into aldehydes and hydroxy-nitrosamines. The longer the alkyl chain, the smaller was the metabolic rate of the α-hydroxylation of alkyl chain yielding aldehyde and the greater was the metabolic rate of the corresponding (ω-1)-hydroxyl metabolite formation. Thus, the (ω-1) hydroxylation of the alkyl chain was the major metabolic pathway of N-nitrosodiamylamine (NDAA) so far as it represented 22-fold the α-hydroxylation. The balance between β to ω hydroxylation and α-hydroxylation depends upon the alkyl chain length and also on specific P450 isoform induction.