Human individuals differ in their capability to metabolize and detoxify drugs and xenobiotics. Cytochrome P-450 (P-450) is a key component of the mixed function oxidase system which metabolizes many drugs and xenobiotics. The type and quantity of specific forms of cytochrome P-450 determine the extent of activation and/or detoxification of particular substrates. Monoclonal antibodies (MAbs) to P-450 were prepared and used for identification and phenotyping of P-450 in tissues and organs of mice, rats and humans by radioimmunoassay (RIA), Western blotting, histochemical staining and inhibitory effects on catalytic activity. When C57BL/6 mice were treated with 3-methylcholanthrene (MC), MC inducible P-450s (MC-P-450s) were identified in liver, lung and kidney but not in those organs of DBA/2 mice. When neonatal rats were treated with the carcinogenic compound 3-nitrofluoranthene, a nitrated product of environmental fluoranthene, MC-P-450s were found to be the predominant forms. In untreated rats, the MC-P-450s were increased during the first month after birth. The MC-P-450s were also identified in human fetal and adult livers. The inducibility of MC-P-450 was modulated by diet and increased by feeding rats a high cholesterol diet. These results indicate that epitope-specific MAbs are very useful probes for identification of P-450s in various tissues and for the study of P-450 changes during development and under different environmental conditions.
