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 alpha-hydroxylation of alkyl chain yielding aldehyde and the greater was the metabolic rate of the corresponding (omega-1)-hydroxyl metabolite formation. Thus, the (omega-1) hydroxylation of the alkyl chain was the major metabolic pathway of N-nitrosodiamylamine (NDAA) so far as it represented 22-fold the alpha-hydroxylation. The balance between beta to omega hydroxylation and alpha-hydroxylation depends upon the alkyl chain length and also on specific P450 isoform induction.