Gamma-Tocopherol-Rich Mixed Tocopherols Inhibit Colon Tumorigenesis in Azoxymethane and Dextran Sulfate Sodium-Treated Mice

We investigated the effects of a γ-tocopherol–rich mixture of tocopherols (γ-TmT, containing 57% γ-T, 24% δ-T, and 13% α-T) on colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)–treated mice. In experiment 1, 6-week-old male CF-1 mice were given a dose of AOM (10 mg/kg body weight, i.p.), and 1 week later, 1.5% DSS in drinking water for 1 week. The mice were maintained on either a γ-TmT (0.3%)–enriched or a standard AIN93M diet, starting 1 week before the AOM injection, until the termination of experiment. In the AOM/DSS–treated mice, dietary γ-TmT treatment resulted in a significantly lower colon inflammation index (52% of the control) on day 7 and number of colon adenomas (9% of the control) on week 7. γ-TmT treatment also resulted in higher apoptotic index in adenomas, lower prostaglandin E2, leukotriene B4, and nitrotyrosine levels in the colon, and lower prostaglandin E2, leukotriene B4, and 8-isoprostane levels in the plasma on week 7. Some of the decreases were observed even on day 7. In experiment 2 with AOM/DSS– treated mice sacrificed on week 21, dietary 0.17% or 0.3% γ-TmT treatment, starting 1 week before the AOM injection, significantly inhibited adenocarcinoma and adenoma formation in the colon (to 17-33% of the control). Dietary 0.3% γ-TmT that was initiated after DSS treatment also exhibited a similar inhibitory activity. The present study showed that γ-TmT effectively inhibited colon carcinogenesis in AOM/DSS–treated mice, and the inhibition may be due to the apoptosis-inducing, anti-inflammatory, antioxidative, and reactive nitrogen species–trapping activities of tocopherols

Effects of Combination of Calcium and Aspirin on Azoxymethane-Induced Aberrant Crypt Foci Formation in the Colons of Mice and Rats

Human intervention studies have suggested an exciting synergistic action between calcium supplementation and aspirin intake in reducing the risk of colorectal cancer. The aim of this study was to determine whether such a synergy can be demonstrated on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) formation in mice and rats. Female CF-1 mice and male F344 rats were injected subcutaneously with AOM and then received diet treatments for 8 wk. The basal control diet contained high fat (20% mixed lipids by weight) and low calcium (1.4 mg/g diet) to mimic the average Western diet. The treatment diets contained enriched calcium (5.2 mg calcium/g diet), aspirin (0.2 mg aspirin/g diet), or calcium plus aspirin (5.2 mg calcium plus 0.2 mg aspirin/g diet). Treatment with calcium, aspirin, or their combination significantly decreased the number of total ACF and aberrant crypt per mouse (by 43-59%) or rat (by 23-38%), but statistically significant differences among the 3 groups were not observed. A hint of additivity between calcium and aspirin was observed in mice but not in rats. These results indicate that the combination of calcium and aspirin did not produce a synergistic effect on the ACF formation in AOM-treated mice and rats