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 facto rs, the intestinal flora (bacteria), and endogenously produced metabol ites contribute to the production of free radicals in the colon, Dieta ry antioxidants, such as vitamin E, should reduce the levels of these harmful oxidation products, In the absence of vitamin E, polyunsaturat ed fats can be oxidized in the colon to produce mutagens, such as lipi d 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 inflamm atory cells in close proximity to the colon can produce reactive nitro gen species (e.g., nitrogen dioxide [NO2]), Increasing evidence sugges ts 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 dif ferent abilities to prevent neoplastic transformation, This review con siders and evaluates recent studies relating vitamin E and oxidative s tress to colon cancer, emphasizing the distinct roles of alpha- and ga mma-tocopherols, In addition, recent findings on the anti-oxidant/pro- oxidant status of the digesta (ingested food) are discussed with respe ct to the use of anti-oxidants in chemoprevention trials for colon can cer.