Previously, we demonstrated that a \#947;-tocopherol-rich mixture of tocopherols (\#947;-TmT containing 57% \#947;-T, 24% \#948;-T, and 13% \#945;-T), at 0.3% in the AIN93M diet, inhibited colon inflammation and carcinogenesis in mice that were treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). The dietary treatment also resulted in lower levels of prostaglandin E2, leukotriene B4, nitrotyrosine, and 8-isoprostane in the colonic tissues and/or plasma of AOM/DSS-treated mice. These results suggest that the inhibition of carcinogenesis is due to the anti-inflammatory, antioxidative, and reactive nitrogen species-trapping activities of \#947;-TmT (Ju et al., Cancer Prev Res, in press). The pure \#947;-tocopherol (\#947;-T) treatment (at 0.17% in the diet), however, did not produce any inhibitory effects against colon adenocarcinoma or adenoma formation in the AOM/DSS-treated mice, even though the treatment significantly increased \#947;-T levels in the plasma, liver, and colon to the levels similar to those of the 0.3% \#947;-TmT-treated mice. The dietary \#947;-T treatment did not significantly change the \#945;-T and \#948;-T levels. In order to compare inhibitory activities of pure and mixture of tocopherols, we conducted another experiment, in which 5-week old male CD-1 mice were treated with 0.3% \#947;-TmT (containing 0.17% \#947;-T), 0.17% \#947;-T, 0.17% \#948;-T, 0.17% mixture of \#947;-T and \#948;-T (at the same ratio of \#947;-T to \#948;-T in the \#947;-TmT) or basal diet (a modified AIN93M diet containing \#945;-T at a level corresponding to the average American dietary intake). One week after the dietary tocopherol treatment was initiated, the mice were given AOM (6 mg/kg body weight, i.p.) twice at 4 days interval, and one week after the second injection of AOM, the mice were given 1.5% DSS in drinking water for 1 week. This experiment was terminated at 14 weeks after DSS treatment. The AOM/DSS-treated mice on the basal diet had 4.4 ± 1.6 tumors per mouse in the colon. Dietary 0.3% \#947;-TmT resulted in a lower number of colon tumors (1.8 ± 0.8), but none of the other tocopherol treatments produced inhibitory effects. These results suggest that a proper quantity and ratio of \#945;-T, \#947;-T and/or \#948;-T is required for optimal anti-carcinogenic activities of \#947;-TmT. Because of the wide occurrence of tocopherols in our diet, and a mixed tocopherol preparation is readily available as dietary supplements, it has a great potential for future use in human cancer prevention (supported by NIH grant CA120915).

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 44.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO