Reactive oxygen species and oxidative DNA damage

Reactive oxygen species (ROS) such as the superoxide anion radical (O2.-) hydrogen peroxide (H2O2) and hydroxyl radical (.OH) have been implicated in the pathophysiology of various states, including ischemia reperfusion injury, haemorrhagic shock, atherosclerosis, heart failure, acute hypertension and cancer. The free radicals, nitric oxide (NO) and O2.- react to form peroxynitrite (ONOO-), a potent cytotoxic oxidant. A potential mechanism of oxidative damage is the nitration of tyrosine residues of protein, peroxidation of lipids, degradation of DNA and oligonucleosomal fragments. Several mechanisms are responsible for the protection of the cells from potential cytotoxic damage caused by free radicals. Cells have developed various enzymatic and nonenzymatic defense systems to control excited oxygen species, however, a certain fraction escapes the cellular defense and may cause permanent or transient damage to nucleic acids within the cells, leading to such events as DNA strand breakage and disruption of Ca2+ metabolism. There is currently great interest in the possible role of ROS in causing DNA damage that leads to cancer and spontaneous mutations. A high rate of oxidative damage to mammalian DNA has been demonstrated by measuring oxidized DNA bases excreted in urine after DNA repair. The rate of oxidative DNA damage is directly related to the metabolic rate and inversely related to life span of the organism.