Cytochromes P-450 as Determinants of Susceptibility to Carcinogenesis by Aromatic Amines and Nitroaromatic Hydrocarbons

Abstract

Aromatic amines and nitroaromatic hydrocarbons represent two major classes of occupational and environmental carcinogens. Aromatic amines are known to be present in the workplace, in cigarette smoke, synthetic fuels, and as pyrolysis products formed during the cooking of foods1–5; while nitroaromatic hydrocarbons have been used as dye intermediates, antimicrobial drugs, and food additives or have been detected as pollutants in coal fly ash, urban air samples, and emissions from auto, diesel, and airplane engines6. Epidemiological studies in humans and carcinogenicity experiments in laboratory animals have clearly indicated that these chemical carcinogens can induce cancers in several tissues, especially the urinary bladder, colon, liver, and lung7. For both aromatic amines and nitroaromatics, metabolic activation is a necessary prerequisite to the formation of carcinogen-DNA adducts; and cytochromes P-450 have been shown to play a major role in this process (reviewed in ref. 8). In this paper, the catalytic activity of specific cytochrome P-450 isozymes for the activation of these carcinogens will be discussed in relation to species and individual differences in cancer susceptibility.