δ- and γ-Tocopherols, but not α-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 delta-tocopherol (delta-T), gamma-T, and alpha-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 delta-T, gamma-T, alpha-T, or a gamma-T-rich mixture of tocopherols (gamma-TmT), until the termination of the experiment at 8 weeks after the second AOM injection. delta-T treatment showed the strongest inhibitory effect, decreasing the numbers of aberrant crypt foci by 62%. gamma-T and gamma-TmT were also effective, but alpha-T was not. Immunohistochemical analysis showed that delta-T and gamma-T treatments reduced the levels of 4-hydroxynonenal and nitrotyrosine and the expression of cyclin D1 in the colon, preserved the expression of PPAR-gamma, and decreased the serum levels of prostaglandin E2 and 8-isoprostane. Supplementation with 0.2% delta-T, gamma-T, or alpha-T increased the respective levels of tocopherols and their side-chain degradation metabolites in the serum and colon tissues. Rather high concentrations of delta-T and gamma-T and their metabolites were found in colon tissues. Our study provides the first evidence for the much higher cancer preventive activity of delta-T and gamma-T than alpha-T in a chemically induced colon carcinogenesis model. It further suggests that delta-T is more effective than gamma-T. Cancer Prev Res; 5(4); 644-54. (C) 2012 AACR.