Tocopherols and the etiology of colon cancer

Colorectal cancer is the second mast common cause of cancer deaths in the United States for both sexes, Considerable evidence suggests that the risk of this cancer is increased by the mutagenic actions of free radicals, which are produced during oxidation reactions, Dietary factors, the intestinal flora (bacteria), and endogenously produced metabolites contribute to the production of free radicals in the colon, Dietary antioxidants, such as vitamin E, should reduce the levels of these harmful oxidation products, In the absence of vitamin E, polyunsaturated fats can be oxidized in the colon to produce mutagens, such as lipid hydroperoxides and malondialdehyde. Furthermore, fecal bacteria can generate a high flux of reactive oxygen species (e.g., the superoxide radical [O-2*(-)]) at the surface of the intestinal lumen, and inflammatory cells in close proximity to the colon can produce reactive nitrogen species (e.g., nitrogen dioxide [NO2]), Increasing evidence suggests that the different chemical (e.g., alpha- and gamma-tocopherol) and stereochemical (e.g., RRR- and all-racemic-alpha-tocopherol) forms of vitamin E have distinct biologic potencies, pharmacokinetics, and different abilities to prevent neoplastic transformation, This review considers and evaluates recent studies relating vitamin E and oxidative stress to colon cancer, emphasizing the distinct roles of alpha- and gamma-tocopherols, In addition, recent findings on the anti-oxidant/pro-oxidant status of the digesta (ingested food) are discussed with respect to the use of anti-oxidants in chemoprevention trials for colon cancer.