Factors influencing the microsome- and mitochondria-catalyzed in vitro binding of diethylnitrosamine and N-nitrosopiperidine to deoxyribonucleic acid

[ 14C]Diethylnitrosamine ([ 14C]DEN) and [ 14C] N-nitrosopiperidine ([ 14]NPiP) bind covalently to calf thymus DNA in an in vitro incubation system containing rat liver microsomes. The reaction is NADPH-dependent. Pretreatment of the animals with phenobarbital (PB) enchances the binding of both DEN and NPiP to DNA, whereas the binding of DEN to DNA decreases after 3-methylcholanthrene pretreatment. The PB effect, as observed from the binding of DEN to DNA. is more pronounced in young rats than in the older animals. Addition of cytosol to the incubation system enhances the binding of DEN 3- to 4-fold and the binding of NPiP 2- to 3-fold. Addition of mitochondria to the incubation system increases the binding of [ 14C]DEN only slighty. but increases the binding of NPiP more than 5-fold. Addition of mitochondria has no effect on the binding of [ 14C]dimethylnitrosamine ([ 14C]DMN). Mitochondria alone markedly catalyze the binding of NPiP to DNA. Addition of benzylamine. which is a substrate of mitochondrial monoamine oxidase as well as an inhibitor of DMN-demethylase, inhibits the binding of NPiP catalyzed by microsomes and microsomes plus mitochondria.