Antibodies as probes of cytochrome P450 isozymes.

Abstract

Cytochrome P450*, an integral membrane protein, is widely distributed in many mammalian tissues, but is present in the highest concentration in hepatic endoplasmic reticulum. It functions as the terminal oxidase of an electron transport system that is involved in the metabolism of a large number of xenobiotics as well as endogenous substrates such as steroids, bile acids, fatty acids and prostaglandins (1). Although this enzyme system formerly was believed to function principally in detoxification, it is now known to metabolically activate many compounds to reactive metabolites that initiate toxic and carcinogenic events (2). Even more interesting is the observation that only certain optical isomers of bay-region diol epoxides of polycyclic aromatic hydrocarbons are carcinogenic, and that the cytochrome P450-dependent mixed function oxidase system preferentially catalyzes the formation of the optical isomer with the highest carcinogenic activity (3).