d- and g-Tocopherols, but not a-Tocopherol, Inhibit Colon Carcinogenesis in Azoxymethane-Treated F344 Rats

The cancer preventive activity of vitamin E has been extensively discussed, but the activities of specific forms of tocopherols have not received sufficient attention. Herein, we compared the activities of d-tocopherol (d-T), g-T, and a-T in a colon carcinogenesis model. Male F344 rats, seven weeks old, were given two weekly subcutaneous injections of azoxymethane (AOM) each at a dose of 15 mg/kg body weight. Starting 1 week before the AOM injection, the animals were maintained on a modified AIN76A diet, or the same diet containing 0.2% of d-T, g-T, a-T, or a g-T-rich mixture of tocopherols (g-TmT), until the termination of the experiment at 8 weeks after the second AOM injection. d-T treatment showed the strongest inhibitory effect, decreasing the numbers of aberrant crypt foci by 62%. g-T and g-TmT were also effective, but a-T was not. Immunohistochemical analysis showed that d-T and g-T treatments reduced the levels of 4-hydroxynonenal and nitrotyrosine and the expression of cyclin D1 in the colon, preserved the expression of PPAR-g , and decreased the serum levels of prostaglandin E2 and 8isoprostane. Supplementation with 0.2% d-T, g-T, or a-T increased the respective levels of tocopherols and their side-chain degradation metabolites in the serum and colon tissues. Rather high concentrations of d-T and g-T and their metabolites were found in colon tissues. Our study provides the first evidence for the much higher cancer preventive activity of d-T and g-T than a-T in a chemically induced colon carcinogenesis model. It further suggests that d-T is more effective than g-T. Cancer Prev Res; 5(4);