Oxidative stress, redox, and the tumor microenvironment

Cellular metabolism is critical for the generation of energy in biological systems; however, as a result of electron transfer reactions, reactive oxygen species (ROS) are generated in aerobic cells. Although low amounts of ROS are easily tolerated by the cell, abnormally high levels of ROS induce oxidative stress. ROS are also produced after exposure to ionizing radiation, selected chemotherapeutic agents, hyperthermia, inhibition of antioxidant enzymes, or depletion of cellular reductants such as NADPH and glutathione. Oxidative stress such as ionizing radiation produces a variety of highly reactive free radicals that damage cells, initiate signal transduction pathways, and alter gene expression. Cells are capable of countering the effects of oxidative stress by virtue of a complex redox buffering system. With respect to the radiation treatment of cancer, components of the cellular redox armamentarium may be targeted to enhance cell killing in the case of tumors and/or protection in the case of normal tissues. © 2004 Elsevier Inc. All rights reserved.