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.