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 and cause oxidative damage to DNA at a rate that is probably a significant contributor to the age-related development of cancer. Agents that decrease oxidative DNA damage should thus decrease the risk of cancer development. That is, oxidative DNA damage is a "biomarker" for identifying persons at risk (for dietary or genetic reasons, or both) of developing cancer and for suggesting how the diets of these persons could be modified to decrease that risk. This biomarker concept presupposes that we can measure oxidative damage accurately in DNA from relevant tissues. Little information is available on whether oxidative DNA damage in blood cells mirrors such damage in tissues at risk of cancer development. Measurement of 8-hydroxylated guanine (eg, as 8-hydroxy-2'-deoxyguanosine; 8OHdG) is the commonest method of assessing DNA damage, but there is no consensus on what the true levels are in human DNA. If the lowest levels reported are correct, 8OHdG may be only a minor product of oxidative DNA damage. Indeed, 8OHdG may be difficult to measure because of the ease with which it is formed artifactually during isolation, hydrolysis, and analysis of DNA. Mass spectrometry can accurately measure a wide spectrum of DNA base damage products, but the development of liquid chromatography-mass spectrometry techniques and improved DNA hydrolysis procedures is urgently required. The available evidence suggests that in Western populations, intake of certain fruit and vegetables can decrease oxidative DNA damage, whereas ascorbate, vitamin E, and beta-carotene cannot.
Halliwell
B
B
Department of Biochemistry, National University of Singapore. bchbh@nus.edu.sg
D000080242:8-Hydroxy-2'-Deoxyguanosine; D014408:Biomarkers, Tumor; D004247:DNA / Q000032:analysis; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D009747:Nutritional Physiological Phenomena; D018384:Oxidative Stress
D014408:Biomarkers, Tumor; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine