THE DUAL ROLES OF NUTRIENTS AS ANTIOXIDANTS AND PROOXIDANTS - THEIR EFFECTS ON TUMOR-CELL GROWTH

The development of a beneficial or a detrimental cellular response by a nutrient will depend on the nutrient's antioxidant or prooxidant cha racteristics, which in turn are a product of the cellular oxygen envir onment. Nutrients such as carotenoids, tocopherols or ascorbate deriva tives will demonstrate an antioxidant or prooxidant characteristic dep ending on the redox potential of the individual molecule and the inorg anic chemistry of the cell. Nutrients acting as chemopreventives, inhi bit the continual growth of transformed clones of cells through their prooxidant activity. In contrast, when an antioxidant activity occurs in transformed cells an enhanced growth may result. In addition, when an inappropriate prooxidant activity develops in normal cells, the rea ctive oxygen metabolites generated could damage the DNA and cellular m embranes. The cellular response is usually a loss of normal regulatory function and activity, depressing cellular intergrity. Therefore, the labile redox character of each nutrient must be considered in terms o f the extracellular and intracellular microoxygen environment. To pred ict if a specific nutrient will have a beneficial or detrimental effec t on a particular tissue or cell, it is important to identify markers that will characterize the biologic activities of each nutrient and el ucidate a possible mechanism of action for that nutrient. In various t issues chemopreventive agents derived from nutrients have been shown i n laboratory animal studies and in some human intervention trials to i nhibit the growth and development of premalignant or malignant lesions . Examples of these tissues include oral tissues, esophagus, gastric c ardia and lung tissues. Recently, some clinical studies demonstrated n o reduction in the incidence of premalignant change, but, to the contr ary, statistical evidence indicated an increase in cancer development. In general, the results of clinical intervention trials remains equiv ocal. The use of chemopreventive agents without considering their phar macologic, oxygen-responsive characteristics will produce unwanted iat rogenic side effects or further cloud evidence of these nutrients' bio logic activities.