Oxidative Damage: DNA Repair and Inducible Resistance

Free radicals and activated oxygen species are generated in a variety of ways. For example, most of the biological effects of ionizing radiations can be ascribed to the oxygen radicals they produce, such as superoxide anion (O₂$$\overline \bullet $$) and hydroxyl radical (·OH) (1). Such radicals are also produced deliberately by macrophages during inflammatory responses, evidently as a means of destroying invading cells (2). It seems likely that the normal reduction of O₂ to water by cytochrome C oxidase might inadvertently release intracellular activated oxygen. Indeed, bacteria devoid of superoxide dismutase, which destroys O₂$$\overline \bullet $$, display a strongly increased spontaneous mutation frequency in aerated but not in hypoxic culture (3). This apparent production of oxygen radicals under normal aerobic conditions underscores the need to understand the nature of the cellular defenses against oxidative damage. We are investigating the mechanisms that cells employ to avert oxidative damage and to correct such damage when it does occur.