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Cytochrome P450-dependent monooxygenases (P450s) are a supergene family of enzymes that catalyse the oxidation of lipophilic chemicals through the insertion of one atom of molecular oxygen into the substrate. They are responsible for the metabolism of a wide range of endogenous and foreign compounds, and in man the transformation of many drugs and chemical carcinogens is mediated by the P450 system (1). It is paradoxical that P450s are involved both in the detoxification of many compounds and also, in some cases, production of the ultimate carcinogen. The major challenge of P450 research is to understand the role that human P450 forms play both separately and together in chemical carcinogenesis, and to determine the relative contribution of genetic and environmental factors in an individual's capacity to metabolize and activate carcinogens. Realization of these goals may identify genes that are important in individual susceptibility to cancer. The purpose of this Commentary is to highlight some of the approaches used in addressing these problems, to discuss both their value and shortcomings, and to suggest possible future advances. Clearly P450s are not the only determinants in chemical carcinogenesis, and other xenobiotic uptake and metabolizing enzymes and DNA repair systems are of considerable importance; many of the approaches adopted to study the P450 system have been or can be applied to these other systems.

Developments and perspectives on the role of cytochrome P450s in chemical carcinogenesis