N-NITROSO COMPOUNDS INDUCE CHANGES IN CARCINOGEN-METABOLIZING ENZYMES

The bioactivation of N-nitrosoamines and polycyclic aromatic hydrocarb ons (PAH) is mediated by the mixed function oxidase system, which incl udes dimethylnitrosamine N-demethylase I (DMN-dI), arylhydrocarbon hyd roxylase (AHH), cytochrome P-450, cytochrome b(5) and NADPH-cytochrome c reductase of liver microsomes. The present study shows the influenc e of N-nitroso compounds on the activities of the above-mentioned enzy mes. Single-dose treatment (20 mg/kg body weight) of male mice with et hylbutylnitrosamine, propylbutylnitrosamine, or dibutylnitrosamine: in creased (1) the activity of DMN-dI by 108%, 104%, 51%, respectively; ( 2) the cytochrome P-450 content by 106%, 72%, 51%, respectively; (3) t he activity of AHH by 95%, 106%, 80% respectively; (4) the cytochrome b(5) content by 164%, 97%, 94% respectively; and (5) decreased the act ivity of NADPH-cytochrome c reductase by 55%, 50% and 45%, respectivel y. Methylpropylnitrosamine decreased the activity of DMN-dI by 44% and the P-450 content by 50%. Diphenylnitrosamine also decreased cytochro me P-450 by 54%, AHH activity by 64% but increased the activity of DMN -dI by 42%, the cytochrome b(5) content by 159% and NADPH-cytochrome c reductase activity by 57%. It seems from this study that the activity of AHH is dependent on P-450 content but DMN-dI is not since the comp ounds that increased or decreased the activity of AHH had parallel eff ects on P-450 content. Also, the extent to which the altered activitie s of DMN-dI, P-450, AHH, cytochrome b(5) and NADPH-cytochrome c reduct ase depends on the type of alkyl groups linked to the nitroso group.