Brief Definitive Report ON THE OCCURRENCE OF CYTOCHROME P-450 AND ARYL HYDROCARBON HYDROXYLASE ACTIVITY IN RAT BRAIN*

Liver microsomes contain a mixed function oxidase system capable of metabolizing a broad range of biologically active substances, including drugs, steroids, and environmental chemicals such as polycyclic hydrocarbons. Certain hemoproteins, collectively referred to as cytochrome P-450, function as the terminal oxidase in this system. The fact that this hepatic mixed function oxidase system is sensitive to induction and inhibition by many of its substrates and other agents has provided an approach to understanding a major mechanism by which endogenouslyand environmentally-derived substances may affect each otheFs disposition and biological impact (1). Mixed function oxidase activities which depend on cytochrome P-450 are present in many tissues other than liver, including such endocrine organs as adrenal, testes, and placenta, such sites of direct xenobiotic exposure as lung, intestine, and skin, and such sites of drug action as heart and kidney. Cytochrome P-450 has also been detected in each of these tissues. Aryl hydrocarbon hydroxylase (AHH) is an example of a mixed function oxidase involving cytochrome P-450 whose distribution and properties have been widely studied. Benzo[a]pyrene (BP), which is a carcinogenic constituent of cigarette smoke and charcoal-broiled meat, is both a substrate and an inducer of this enzyme activity. Because many of the substrates of the hepatic cytochrome P-450 system have major actions on the central nervous system, this study was undertaken to determine whether this cytochrome, and the related AHH activity, could be detected in brain.