Methods to detect DNA damage by free radicals: relation to exercise

Epidemiological investigations repeatedly show decreased morbidity from reg ular exercise compared with sedentary life. A large number of investigation s have demonstrated increased oxidation of important cellular macromolecule s, whereas other investigators have found no effects or even signs of lower ing of oxidation of macromolecules. In particular, extreme and long-duratio n strenuous exercise appears to lead to deleterious oxidation of cellular m acromolecules. The oxidation of DNA is important because the oxidative modi fications of DNA bases, particularly the 8-hydroxylation of guanine, are mu tagenic and have been implicated in a variety of diseases such as ageing an d cancer. The methodologies for further investigation of the relationship b etween DNA oxidation and exercise are available. The preferred methods rely on HPLC or GC-mass spectrometry; whereas the theoretically-attractive liqu id chromatography-tandem mass spectrometry is being developed. Caution shou ld be taken to avoid artifacts because of the six orders of magnitude of di fference between oxidized and non-oxidized DNA bases in tissues. The method s can be used to estimate tissue levels, i.e. a local concentration of oxid ized DNA, or to estimate the rate of body DNA oxidation by the urinary outp ut of repair products, the latter being a method that is independent of rep air. During exercise there appears to be a shifting of dietary-dependent an tioxidant, e.g. vitamin C and vitamin E, from muscle to plasma, and an incr eased oxidation in plasma of these antioxidants. Supplementation trials wit h antioxidants have not been able to increase exercise performance; however , optimum nutrition with antioxidants and possibly supplementation, could b e important in the prevention of diseases in the long term. The pattern fro m these observations appears to be quite consistent; immediately after exer cise, regardless of how intense, there do not appear to be any signs of oxi dative damage to DNA. Acute or prolonged moderate exercise does not produce signs of oxidative DNA damage and might even be associated with lowering o f the levels of oxidation of tissue DNA; however, after long-duration and i ntense exercise an increase in oxidative DNA modifications is apparent. We suggest as a hypothesis that the relationship between exercise and health i s U shaped. This hypothesis needs to be tested in detail in order to establ ish the maximum beneficial exercise level with regard to oxidative DNA modi fication, and also the level that could be deleterious and might even incre ase the risk for cancer and other diseases.