Increased dietary vitamin A, vitamin E, and Beta-carotene have been individually associated with a decreased risk of carcinogen-caused cancer. Consequently, vitamins A and E, and Beta-carotene are considered potential cancer chemopreventive dietary supplements. The data in this proposal show that vitamin E has a regulatory effect on systemic vitamin A metabolism. Vitamin E may also modulate Beta-carotene (provitamin A) conversion to vitamin A. This application will study the extent and mechanisms of vitamin E regulation of vitamin A homeostasis. Thus, the steady-state pools of vitamin A and its metabolites in rat blood and tissues will be measured and compared as a function of dietary vitamin E by high-performance liquid chromatography (HPLC). These data will direct attention to the enzymes of vitamin A metabolism modified by vitamin E. Assays will be set-up in vitro to study the vitamin E effects with respect to: mechanism of action; structure-activity relationships; effectiveness of antioxidants; and sensitivity of alternate substrates. Gas chromatographic/mass spectral, and HPLC assays will be developed for vitamin A and its metabolites whose in vivo concentrations are dependent upon dietary vitamin E. These assays will be used to monitor changes in vitamin A metabolites as a function of dietary vitamin E with Beta-carotene rather than retinyl palmitate as the dietary vitamin A source; and with diets high in polyunsaturated fatty acids (PUFA). These studies would outline the metabolic interactions among vitamins A and E, Beta-carotene, and PUFA. The data would provide the basis for rational dietary supplementation recommendations, and define one determinant of vitamin A homeostasis. The methodology developed will be useful in further studies of other vitamin A homeostasis determinants.
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