INDUCIBILITY OF HUMAN CYTOCHROMES P-450 PRIMARILY INVOLVED IN THE ACTIVATION OF CHEMICAL CARCINOGENS

Of least 20 different cytochromes P-450 (CYPs) that have been found in human tissues, only 4 of these thus far have been shown to contribute to carcinogen metabolism to a major extent. There is wide interindividual variability for these CYP's in human populations that appear to arise from both genetic and environmental factors. CYP2E1, which catalyzes the oxidation of many low molecular weight compounds, including nitrosamines, halogenated hydrocarbons, and vinyl derivatives, is known to be inducible in humans by alcohol and is elevated in diabetics. CYP3A4, which plays a major role in the activation of mycotoxins, pyrrolizidine alkaloids, and some aromatic amines, is inducible in humans by certain glucocorticoids and antibiotics. CYP1A1 and CYP1A2, which have been well-studied in animals as dioxin-inducible enzymes, are induced in humans by cigarette smoke and polyhalogenated biphenyls; and the latter is also induced by charbroiled meats, cruciferous vegetables, and the drug omeprazole. CYP1A1 appears to be important in polycyclic hydrocarbon activation, while CYP1A2 is primarily responsible for the N-oxidation of most carcinogenic aromatic and heterocyclic amines.