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Abstract

Low vitamin E nutritional status has been suggested to increase cancer risk. However, recent large-scale human trials with high doses of alpha-tocopherol (α-T) have produced disappointing results. This points out the need for a better understanding of the biological activities of different forms of tocopherols. Using a tocopherol mixture that is rich in γ-T (γ-TmT), we demonstrated the inhibition of colon carcinogenesis in mice, and the inhibition is associated with decreased levels of 8-isoprostane, nitrotyrosine, prostaglandin E2 and leukotriene B4. Dietary 0.3% γ-TmT also inhibited chemically induced lung tumorigenesis in the A/J mice as well as the growth of lung cancer cells in xenograft or allograft tumors; the inhibition was associated with a reduction of oxidative/nitrosative stress. δ-T was found to be more active than γ-T in the inhibition of cancer cell growth in culture and lung cancer xenograft tumors as well as in azoxymethane-induced colon aberrant crypt foci formation in rats, whereas α-T was ineffective. Analysis of the levels of tocopherols and their metabolites in blood and tissues suggests that metabolites of δ-T and γ-T contribute to their inhibitory activity. These studies demonstrate the broad cancer preventive activity of γ-TmT and higher activity of δ-T.

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