Why and how should we measure oxidative DNA damage in nutritional studies?How far have we come?

Free radicals and other reactive species are constantly generated in vivo a nd cause oxidative damage to DNA at a rate that is probably a significant c ontributor to the age-related development of cancer. Agents that decrease o xidative DNA damage should thus decrease the risk of cancer development. Th at is, oxidative DNA damage is a "biomarker" for identifying persons at ris k (for dietary or genetic reasons, or both) of developing cancer and for su ggesting how the diets of these persons could be modified to decrease that risk. This biomarker concept presupposes that we can measure oxidative dama ge accurately in DNA from relevant tissues. Little information is available on whether oxidative DNA damage in blood cells mirrors such damage in tiss ues at risk of cancer development. Measurement of 8-hydroxylated guanine le g, as 8-hydroxy-2'-deoxyguanosine; 8OHdG) is the commonest method of assess ing DNA damage, but there is no consensus on what the true levels are in hu man DNA. If the lowest levels reported are correct, 8OHdG may be only a min or product of oxidative DNA damage. Indeed, 8OHdG may be difficult to measu re because of the ease with which it is formed artifactually during isolati on, hydrolysis, and analysis of DNA. Mass spectrometry can accurately measu re a wide spectrum of DNA base damage products, but the development of liqu id chromatography-mass spectrometry techniques and improved DNA hydrolysis procedures is urgently required. The available evidence suggests that in We stern populations, intake of certain fruit and vegetables can decrease oxid ative DNA damage, whereas ascorbate, vitamin E, and beta -carotene cannot.