Zhang P, Omaye S T
Environmental Sciences and Health Graduate Program, Mail Stop 142, University of Nevada, Reno, NV 89557, USA.
Toxicol In Vitro. 2001 Feb;15(1):13-24. doi: 10.1016/s0887-2333(00)00054-0.
Experiments were conducted to determine the antioxidant and prooxidant effects of beta-carotene, alpha-tocopherol and ascorbic acid on human lung cells at different oxygen (O(2)) tensions. Free radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), was used to induce the cellular damage associated with lipid peroxidation, protein oxidation and DNA breaks. Under hypoxic conditions (0 torr O(2) tension) all compounds produced a concentration-dependent antioxidant effect. Mixtures of the three compounds exhibited greater protective affects than any individual compound. At 143 torr O(2) tension, all compounds exhibited concentration-dependent protective effects against AAPH-induced cellular lipid, protein and DNA damage. At 722 torr O(2) tension, cells exhibited a consistent increase in lipid peroxidation (isoprostane formation), protein oxidation (carbonyl formation) and DNA damage (p53 protein accumulation). beta-Carotene (1.5 microM) produced a prooxidant effect by promoting 12% isoprostane formation. Protein oxidation and DNA damage at 722 torr O(2) tension was not increased by beta-carotene; however, the antioxidant effect of beta-carotene was attenuated. The antioxidant effects of alpha-tocopherol, ascorbic acid, and mixtures of the three antioxidant compounds also were reduced by the high O(2) conditions. These results partially substantiate the hypothesis that the antioxidant and prooxidant effects of beta-carotene are dependent on O(2) tension and concentration of beta-carotene. Such findings may partially explain why selected populations, such as smokers, respond adversely when supplemented with beta-carotene.
开展实验以确定β-胡萝卜素、α-生育酚和抗坏血酸在不同氧（O₂）张力下对人肺细胞的抗氧化和促氧化作用。使用自由基引发剂2,2'-偶氮二（2-脒基丙烷）二盐酸盐（AAPH）诱导与脂质过氧化、蛋白质氧化和DNA断裂相关的细胞损伤。在低氧条件下（0托O₂张力），所有化合物均产生浓度依赖性的抗氧化作用。三种化合物的混合物表现出比任何单一化合物更强的保护作用。在143托O₂张力下，所有化合物均表现出浓度依赖性的保护作用，可抵抗AAPH诱导的细胞脂质、蛋白质和DNA损伤。在722托O₂张力下，细胞的脂质过氧化（异前列腺素形成）、蛋白质氧化（羰基形成）和DNA损伤（p53蛋白积累）持续增加。β-胡萝卜素（1.5微摩尔）通过促进12%的异前列腺素形成产生促氧化作用。在722托O₂张力下，β-胡萝卜素并未增加蛋白质氧化和DNA损伤；然而，β-胡萝卜素的抗氧化作用减弱。高氧条件也降低了α-生育酚、抗坏血酸以及这三种抗氧化化合物混合物的抗氧化作用。这些结果部分证实了以下假设：β-胡萝卜素的抗氧化和促氧化作用取决于O₂张力和β-胡萝卜素的浓度。这些发现可能部分解释了为何某些特定人群，如吸烟者，在补充β-胡萝卜素时会产生不良反应。
