Epidemiologic evidence linking dietary carotenoid intake to a reduced risk of lung cancer and other diseases has led to widespread use of beta-carotene containing vitamins and food supplements. Results of recent randomized cancer prevention trials appear contradictory and in the largest trial to date, beta- carotene increased lung cancer incidence in smokers. The current confusion underscores the lack of understanding of carotenoid actions at the molecular chemical level. Carotenoids are thought to prevent carcinogenic tissue damage by trapping free radicals in cigarette smoke, but they also may express potentially damaging prooxidant behavior at the high oxygen tensions typically found in the lung. This project will test the hypothesis that prooxidant actions of beta-carotene enhance oxidative damage caused by smoke borne oxidants. Antioxidant reactions trap smoke borne oxidants and prevent damage, whereas other interactions may promote beta-carotene autoxidation, which may lead to enhanced oxidation of other tissue components. The overall objective of the project is to determine how interactions between different smoke components and beta-carotene govern the prooxidant antioxidant balance of beta-carotene action.
The Specific Aims of the project are: 1) to identify the oxidative fate of beta-carotene consumed by cigarette smoke induced oxidation in model chemical and liposomal systems; 2) to determine the effect of beta-carotene on the oxidation of lipids in chemical model systems exposed to cigarette smoke; and 3) to determine the effect of beta-carotene on the oxidation of cellular lipids, DNA, and other cellular antioxidants in human bronchial epithelial cells exposed to whole cigarette smoke or to smoke fractions.
|Arora, A; Willhite, C A; Liebler, D C (2001) Interactions of beta-carotene and cigarette smoke in human bronchial epithelial cells. Carcinogenesis 22:1173-8|
|Baker, D L; Krol, E S; Jacobsen, N et al. (1999) Reactions of beta-carotene with cigarette smoke oxidants. Identification of carotenoid oxidation products and evaluation of the prooxidant/antioxidant effect. Chem Res Toxicol 12:535-43|
|Liebler, D C; Stratton, S P; Kaysen, K L (1997) Antioxidant actions of beta-carotene in liposomal and microsomal membranes: role of carotenoid-membrane incorporation and alpha-tocopherol. Arch Biochem Biophys 338:244-50|
|Stratton, S P; Liebler, D C (1997) Determination of singlet oxygen-specific versus radical-mediated lipid peroxidation in photosensitized oxidation of lipid bilayers: effect of beta-carotene and alpha-tocopherol. Biochemistry 36:12911-20|
|Liebler, D C; McClure, T D (1996) Antioxidant reactions of beta-carotene: identification of carotenoid-radical adducts. Chem Res Toxicol 9:8-11|
|McClure, T D; Liebler, D C (1995) A rapid method for profiling the products of antioxidant reactions by negative ion chemical ionization mass spectrometry. Chem Res Toxicol 8:128-35|
|Stratton, S P; Schaefer, W H; Liebler, D C (1993) Isolation and identification of singlet oxygen oxidation products of beta-carotene. Chem Res Toxicol 6:542-7|
|Liebler, D C (1993) Antioxidant reactions of carotenoids. Ann N Y Acad Sci 691:20-31|