A γ-Tocopherol–Rich Mixture of Tocopherols Inhibits Colon Inflammation and Carcinogenesis in Azoxymethane and Dextran Sulfate Sodium–Treated Mice

Abstract

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.