Mechanism and control of denitrosation of N-nitrosodimethylamine.

Abstract

The NADPH-dependent microsomal denitrosation of N-nitrosodimethylamine (NDMA) has been investigated using a new procedure which was devised for the determination of nitric oxide under aerobic conditions. On the basis of the results obtained with rat-liver microsomes it is concluded that nitric oxide is formed as a precursor of nitrite in a superoxide dismutase (SOD)-insensitive reaction. The enzyme involved in the denitrosation was found to correspond to the cytochrome P450 isoenzyme responsible for the dealkylation of NDMA. The chemical mechanism of the liberation of nitric oxide is proposed to be of an oxidative nature.