HYDROXYLATION OF CARBON-ATOMS OF THE ALKYL CHAIN OF SYMMETRICAL N-NITROSODIALKYLAMINES BY RAT-LIVER MICROSOMES

Liver microsomal preparations from control and treated rats (cytochrom es P450 1A, 2B, 3A and 2E1-induced) metabolized at variable metabolic rates three nitrosodialkylamines (N-nitroso-dipropyl, dibutyl and diam yl-amines) into aldehydes and hydroxy-nitrosamines. The longer the alk yl chain, the smaller was the metabolic rate of the cu-hydroxylation o f alkyl chain yielding aldehyde and the greater was the metabolic rate of the corresponding (omega-1)-hydroxyl metabolite formation. Thus, t he (omega-1) hydroxylation of the alkyl chain was the major metabolic pathway of N-nitrosodiamylamine (NDAA) so far as it represented 22-fol d the alpha-hydroxylation. The balance between beta to omega hydroxyla tion and alpha-hydroxylation depends upon the alkyl chain length and a lso on specific P450 isoform induction.