Antioxidant and prooxidant roles for β-carotene, α-tocopherol and ascorbic acid in human lung cells

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 muM) 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. (C) 2001 Elsevier Science Ltd. All rights reserved.