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 characteristics, which in turn are a product of the cellular oxygen environment. Nutrients such as carotenoids, tocopherols or ascorbate derivatives will demonstrate an antioxidant or prooxidant characteristic depending on the redox potential of the individual molecule and the inorganic chemistry of the cell. Nutrients acting as chemopreventives, inhibit 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 reactive oxygen metabolites generated could damage the DNA and cellular membranes. The cellular response is usually a loss of normal regulatory function and activity, depressing cellular integrity. Therefore, the labile redox character of each nutrient must be considered in terms of the extracellular and intracellular microoxygen environment. To predict if a specific nutrient will have a beneficial or detrimental effect on a particular tissue or cell, it is important to identify markers that will characterize the biologic activities of each nutrient and elucidate a possible mechanism of action for that nutrient. In various tissues chemopreventive agents derived from nutrients have been shown in laboratory animal studies and in some human intervention trials to inhibit the growth and development of premalignant or malignant lesions. Examples of these tissues include oral tissues, esophagus, gastric cardia and lung tissues. Recently, some clinical studies demonstrated no reduction in the incidence of premalignant change, but, to the contrary, statistical evidence indicated an increase in cancer development. In general, the results of clinical intervention trials remains equivocal. The use of chemopreventive agents without considering their pharmacologic, oxygen-responsive characteristics will produce unwanted iatrogenic side effects or further cloud evidence of these nutrients' biologic activities.