Cytochrome P-450s metabolize xenobiotics such as drugs and carcinogens, as well as endobiotics such as steroids and prostaglandins. Multiple forms of these enzymes are expressed constitutively or after administration of inducers. A single cytochrome P-450 may metabolize multiple substrates and a single substrate may be acted upon by either a single or several cytochrome P-450s. Cytochrome P-450s may engage normal detoxification or catalyze deleterious carcinogen or mutagen activation. This project has used previously cloned cDNAs of P-450s to construct cDNAs into vaccinia virus vectors. These vectors express the incorporated cDNA into a single P-450 enzyme when infected into host cells. This approach measures the substrate and product specificity of a single P-450. The second approach is complementary to the latter and uses inhibitory Mabs to measure the contribution of a single P-450 to the total activity of a tissue. These two approaches have been widely applied to the metabolism and mutagen activation of a variety of drugs and environmental agents.
