Cytochromes P-450 are the key components of the mixed-function oxidase system which metabolizes most chemical carcinogens, including benzo(a)pyrene, aflatoxin, nitrosamine and protein-pyrolysates. Specific forms of cytochromes P-450 are responsible for the activation and disposition of chemical carcinogens. Therefore, identification and quantitation of cytochrome P-450 isozymes are essential to understand the role of cytochrome P-450 in the primary stages of chemical carcinogenesis and in individual differences in sensitivity to chemical carcinogens. Our approach is to prepare and use monoclonal antibodies (MAbs) as specific probes for individual and classes of cytochrome P-450. Panels of MAbs have been prepared to cytochromes P-450 of rats treated with phenobarbital, 3-methylcholanthrene, pregnenolone 16-Alpha-carbonitrile and ethanol, and an environmentally induced cytochrome P-450 in fish (scup). These Mabs are characterized for their epitope specificity toward different cytochrome P-450 isozymes. A MAb to the fish cytochrome P-450 cross-reacts with 3-methylcholanthrene-inducible rat cytochrome P-450 and may be useful for monitoring polluted marine environments. MAbs to an ethanol-inducible and nitrosamine metabolizing cytochrome P-450 (P450et) have been utilized for identification of P-450et in liver microsomal preparations of rats which were untreated or treated with different chemical agents.
