DNA strand breakage and oxygen tension:: effects of β-carotene, α-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 muM) was examined under different O-2 tensions and with other antioxidants: alpha -tocopherol (5-80 muM), ascorbic acid (10-160 muM) 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 tinder 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 H aa achieved in the mixture of antioxidants. Under 150 torr of oxygen tension, the antioxidant effect of beta -carotene was diminished at greater than or equal to 0.8 muM. A prooxidant effect was found at 0.8 greater than or equal to muM 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 muM 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. (C) 2001 Elsevier Science Ltd. All rights reserved.