New careers for antioxidants

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Abstract
It is a remarkable fact that antioxidants are nontoxic compounds that reduce the incidence of cancer. Antioxidant nutrients such as vitamin E, β-carotene, lycopene, and selenium are regularly found to reduce the risk of lung, prostate, stomach, or total cancers, as well as oral precancers, in epidemiologic studies (1). Foods containing these nutrients are similarly effective, as are nondietary antioxidants such as green tea phenols and various Oriental herbal medicines (2). In general, the level of risk reduction is on the order of 0.6, which might encouragingly be extrapolated to (0.6)n for those of us with n organs at risk. The risk reduction from an antioxidant can be 3-fold in the elderly, in smokers, and in subpopulations deficient in a second antioxidant (1). This result suggests that functional redundancy of antioxidant systems is hiding the importance of their biological roles until two actors have been removed, as often happens with gene knockouts. These nutrients, as well as nonnutrient antioxidants such as N-acetyl cysteine, also slow the appearance of tumors in mice (2–4). Why do antioxidants have these effects? Biochemically, attention has traditionally centered on the obvious suspect, the ability of these compounds to scavenge free radicals, especially reactive oxygen species. Lipid-soluble antioxidants such as vitamin E act as chain-breakers to stop the propagation of sequential free radical reactions, as can water-soluble antioxidants such as vitamin C. Eradicating radicals will reduce damage to DNA and membranes (Fig. 1). But antioxidants have other molecular consequences, including inhibiting generation of reactive oxygen species, inhibiting metabolic activation of carcinogens, and altering the intracellular redox potential (5). The latter occurs with those water-soluble antioxidants having a high reducing potential, such as vitamin C and N-acetyl cysteine, which change the cell's redox state. Redox state, in turn, regulates the activity of many transcription …