AuthorKennedy, Todd Allen
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PublisherThe University of Arizona.
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AbstractThe provitamin A carotenoid β-carotene is an attractive candidate for the prevention of cancer. Indeed, abundant evidence suggests that β-carotene inhibits carcinogenesis. β-Carotene is thought to inhibit carcinogenesis by scavenging free radicals involved in tumor formation. However, there is no direct evidence that β-carotene traps radicals under conditions where it inhibits carcinogenesis. The overall objective of this dissertation research was to identify β-carotene oxidation products from β-carotene antioxidant reactions in model systems. Identification of such products will enable the direct measurement of β-carotene antioxidant activity in systems where it inhibits neoplastic transformation. In hexane solution, β-carotene was oxidized by peroxyl radicals to 5,6-epoxy-β, β-carotene, 15,15'-epoxy-β, β-carotene, a previously unreported product, and several unidentified polar products. Studies on the kinetics of product formation suggested that polar products are formed by both epoxide-dependent and -independent pathways. Because β-carotene may be localized within lipid bilayers in vivo, peroxyl radical oxidation of β-carotene in model membranes was examined. In soy phosphatidylcholine liposomes, β-carotene was oxidized by peroxyl radicals to the 5,6-epoxide and to unidentified polar products. β-Carotene antioxidant activity in the liposome system was the same at 15 torr and 160 torr O₂ and decreased at 760 torr O₂. These results suggest that β-carotene provides equal antioxidant protection in all tissues in vivo. The relative rates of product formation and β-carotene oxidation at different pO₂ suggested that β-carotene antioxidant activity is governed by the relative proportions of β-carotene radical trapping and autoxidation reactions, which do not contribute to radical trapping. Therefore, the loss of β-carotene antioxidant action at 760 torr O₂ may result from an increase in β-carotene oxidation by autoxidation pathways. The 5,6-epoxide was formed during both antioxidant reactions and autoxidation reactions and may be marker for the peroxyl radical oxidation of β-carotene. Attempts to study β-carotene antioxidant reactions in biological membranes were only partially successful. In vitro incorporation of β-carotene into microsomes was attempted by several methods. However, these efforts resulted in only modest β-carotene antioxidant activity in microsomes. These studies provide a basic understanding of β-carotene antioxidant chemistry in model systems. Their results will enable further investigation of β-carotene antioxidant action in biological systems.
Degree ProgramPharmacology & Toxicology