The effects of antioxidants on skin tumor initiation and aryl hydrocarbon hydroxylase.
Butylated hydroxytoluene, butylated hydroxyanisole, and vitamins C and E are effective inhibitors of 7,12-dimethylbenz(a)anthracene tumor initiation in a two-stage system of tumorigenesis. These antioxidants did not significantly induce epidermal aryl hydrocarbon [benzo(a)pyrene]hydroxylase, nor did they have any effect when added directly to the in vitro aryl hydrocarbon [benzo(a)pyrene]hydroxylase assay. However, butylated hydroxytolene and butylated hydroxyanisole, when topically to mice, inhibited the in vitro, epidermally mediated, covalent binding of radioactive benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene to DNA. When butylated hydroxytolene and butylated hydroxyanisole were added in vitro, they did not inhibit the epidermally mediated covalent binding of the hydrocarbons to DNA. The inhibition of polycyclic hydrocarbon tumorigenesis by antioxidants may be related to the ability of antioxidants to prevent the in vivo activation of hydrocarbons to carcinogenic epoxides and/or other electrophilic intermediates or may be related to their ability to increase detoxification of the reactive intermediate that requires intact cells to be operational. In any event, the results suggest that the antioxidants have an indirect effect on the epidermal metabolizing system which leads to a decrease in covalent binding to DNA.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors*; D000287:Administration, Topical; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000378:metabolism*; D001205:Ascorbic Acid / Q000494:pharmacology; D001551:Benz(a)Anthracenes / Q000037:antagonists & inhibitors*; D001580:Benzopyrenes / Q000037:antagonists & inhibitors*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D005419:Flavonoids; D014810:Vitamin E; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases; D001205:Ascorbic Acid