Cytochrome P-450 enzymes as targets for chemoprevention against chemical carcinogenesis and toxicity: opportunities and limitations.

It is well established that most chemical carcinogens require met abolic activation before exerting their carcinogenic effects. The acti vated carcinogens are usually electrophilic agents and are highly reactive toward DNA molecules. DNA modifications, especially those on oncogenes and tumor suppressor genes, are generally major driving forces for cancer development. In theory, chemical carcinogenesis can be prevented, in most cases, by blocking the metabolic activation process. Since cytochrome P450 enzymes play key roles in the acti vation of most carcinogens (1, 2), the inhibition of P4504-dependent