N-nitroso compounds induce changes in carcinogen-metabolizing enzymes.
The bioactivation of N-nitrosoamines and polycyclic aromatic hydrocarbons (PAH) is mediated by the mixed function oxidase system, which includes dimethylnitrosamine N-demethylase I (DMN-dI), arylhydrocarbon hydroxylase (AHH), cytochrome P-450, cytochrome b5 and NADPH-cytochrome c reductase of liver microsomes. The present study shows the influence of N-nitroso compounds on the activities of the above-mentioned enzymes. Single-dose treatment (20 mg/kg body weight) of male mice with ethylbutylnitrosamine, propylbutylnitrosamine, or dibutylnitrosamine: increased (1) the activity of DMN-dI by 108%, 104%, 51%, respectively; (2) the cytochrome P-450 content by 106%, 72%, 51%, respectively; (3) the activity of AHH by 95%, 106%, 80% respectively; (4) the cytochrome b5 content by 164%, 97%, 94% respectively; and (5) decreased the activity of NADPH-cytochrome c reductase by 55%, 50% and 45%, respectively. Methylpropylnitrosamine decreased the activity of DMN-dI by 44% and the P-450 content by 50%. Diphenylnitrosamine also decreased cytochrome P-450 by 54%, AHH activity by 64% but increased the activity of DMN-dI by 42%, the cytochrome b5 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 compounds that increased or decreased the activity of AHH had parallel effects on P-450 content. Also, the extent to which the altered activities of DMN-dI, P-450, AHH, cytochrome b5 and NADPH-cytochrome c reductase depends on the type of alkyl groups linked to the nitroso group.
Sheweita
S A
SA
Department of Environmental Studies, Alexandria University, Egypt.
Mostafa
M H
MH
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects; D002273:Carcinogens / Q000378:metabolism*; D015786:Cytochromes b5 / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009603:Nitroso Compounds / Q000633:toxicity*; D013329:Structure-Activity Relationship
D002273:Carcinogens; D009603:Nitroso Compounds; D015786:Cytochromes b5; D001189:Aryl Hydrocarbon Hydroxylases