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.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000378:metabolism; D002273:Carcinogens / Q000037:antagonists & inhibitors; D003022:Clotrimazole / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004610:Ellagic Acid / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control
D002273:Carcinogens; D004610:Ellagic Acid; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D003022:Clotrimazole