DNA strand breakage and oxygen tension: effects of beta-carotene, alpha-tocopherol and ascorbic acid.
DNA damage is involved in carcinogenesis, aging and other degenerative diseases. The relationship between DNA strand breakage and beta-carotene (0.1-1.6 microM) was examined under different O(2) tensions and with other antioxidants: alpha-tocopherol (5-80 microM), ascorbic acid (10-160 microM) and mixtures of these antioxidants. Supercoiled plasmid DNA pBR322 was incubated with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) to induce DNA strand breaks in the presence of antioxidants under 15, 150, and 760 torr of O(2) tension. Under 15 torr of O(2) tension, beta-carotene, alpha-tocopherol, ascorbic acid and mixtures of these antioxidants provided a dose-dependent protection against AAPH-induced DNA strand breaks. The best protection was achieved in the mixture of antioxidants. Under 150 torr of oxygen tension, the antioxidant effect of beta-carotene was diminished at > or = 0.8 microM. A prooxidant effect was found at 0.8 > or = microM beta-carotene, producing more single- and double-strand breaks. alpha-Tocopherol and ascorbic acid exhibited dose-dependent antioxidant effects at 150 torr of oxygen tension. Under 760 torr of O(2) tension, the prooxidant effect of 0.8 microM beta-carotene was significant, causing supercoiled DNA to completely breakdown to circular and linear forms. In addition, 760 torr of O(2) tension attenuated the antioxidant effects of alpha-tocopherol and ascorbic acid. Thus, beta-carotene causes concentration-dependent DNA breakdown at high O(2) tension. The protection of DNA from the prooxidant effects of beta-carotene afforded by alpha-tocopherol and/or ascorbic acid was limited at high O(2) tension.
Environmental Sciences and Health Graduate Program, Mail Stop 142, University of Nevada, Reno, NV 89557, USA.
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D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D004278:DNA, Superhelical / Q000187:drug effects; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D014810:Vitamin E / Q000494:pharmacology*; D019207:beta Carotene / Q000494:pharmacology*
D000975:Antioxidants; D004278:DNA, Superhelical; D019207:beta Carotene; D014810:Vitamin E; D001205:Ascorbic Acid; D010100:Oxygen