Biphasic effects of dietary antioxidants on oxidative stress-mediated carcinogenesis

There is now strong evidence implicating the generation of reactive oxygen species (ROS) and the corresponding response to oxidative stress as key factors in the pathogenesis of several human diseases including cancer, atherosclerosis, and neurodegenerative disorders, and in ageing. The carcinogenicity of oxidative stress is primarily attributable to the genotoxicity of ROS, but ROS can promote cancer through diverse cellular processes. Therefore, dietary or pharmaceutical augmentation of the endogenous antioxidant defense capacity has been considered a plausible way to prevent ROS-mediated carcinogenicity, but actual antioxidant therapies have been equivocal at best. In fact, most free-radical scavengers act in reversible oxidation-reduction reactions, and some antioxidants can act both as antioxidants and prooxidants, depending on their structures and the conditions. This article summarizes the possible cancer-preventive and -enhancing mechanisms of dietary antioxidants, with an emphasis on epigenetic mechanisms. (c) 2006 Elsevier Ireland Ltd. All rights reserved.