Pharmacological modification of epidermal detoxification systems.

The skin is a major interface between the body and the environment and possesses membrane-bound cytochrome P-450-dependent enzyme activity that is capable of both detoxifying endogenous and exogenous substrates and enhancing the toxic effects of selected substances. The use of chemical inhibitors of enzyme activation by P-450-dependent enzymes represents one possible approach to controlling toxic responses in target tissue such as the skin. Our data indicate that certain polyphenols and imidazoles are potent inhibitors of epidermal carcinogen metabolism, and of the DNA binding and the carcinogenicity of PAHs such as BP. The use of such agents may offer a novel approach to the prevention of environmentally induced cancer.