Zhang P, Omaye S T
Environmental Sciences and Health Graduate Program, Mail Stop 142, University of Nevada, Reno, NV 89557, USA.
Food Chem Toxicol. 2001 Mar;39(3):239-46. doi: 10.1016/s0278-6915(00)00131-9.
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.
DNA损伤与癌症发生、衰老及其他退行性疾病相关。我们研究了在不同氧张力条件下，DNA链断裂与β-胡萝卜素（0.1 - 1.6微摩尔）以及其他抗氧化剂：α-生育酚（5 - 80微摩尔）、抗坏血酸（10 - 160微摩尔）及其混合物之间的关系。将超螺旋质粒DNA pBR322与2,2'-偶氮二（2-脒基丙烷）二盐酸盐（AAPH）一起孵育，在15、150和760托的氧张力下，于抗氧化剂存在的情况下诱导DNA链断裂。在15托的氧张力下，β-胡萝卜素、α-生育酚、抗坏血酸及其混合物对AAPH诱导的DNA链断裂提供了剂量依赖性保护。抗氧化剂混合物提供了最佳保护。在150托的氧张力下，β-胡萝卜素在≥0.8微摩尔时抗氧化作用减弱。在0.8≥微摩尔β-胡萝卜素时发现有促氧化作用，产生更多的单链和双链断裂。α-生育酚和抗坏血酸在150托的氧张力下表现出剂量依赖性抗氧化作用。在760托的氧张力下，0.8微摩尔β-胡萝卜素的促氧化作用显著，导致超螺旋DNA完全分解为环状和线性形式。此外，760托的氧张力减弱了α-生育酚和抗坏血酸的抗氧化作用。因此，在高氧张力下，β-胡萝卜素会导致浓度依赖性的DNA分解。在高氧张力下，α-生育酚和/或抗坏血酸对β-胡萝卜素促氧化作用的DNA保护作用有限。
