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 β-carotene (0.1–1.6 μ m) was examined under different O 2 tensions and with other antioxidants: α-tocopherol (5–80 μ m), ascorbic acid (10–160 μ m) 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, β-carotene, α-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 β-carotene was diminished at ⩾0.8 μ m. A prooxidant effect was found at 0.8⩾μ m β-carotene, producing more single- and double-strand breaks. α-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 μ m β-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 α-tocopherol and ascorbic acid. Thus, β-carotene causes concentration-dependent DNA breakdown at high O 2 tension. The protection of DNA from the prooxidant effects of β-carotene afforded by α-tocopherol and/or ascorbic acid was limited at high O 2 tension.