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Why and how should we measure oxidative DNA damage in nutritional studies? How far have we come?
1Department of Biochemistry, National University of Singapore. bchbh@nus.edu.sg
Abstract:
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.
Insights
Oxidative DNA damage contributes to age-related cancer. While measuring this damage is challenging, certain fruits and vegetables may reduce risk, unlike common antioxidant supplements.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Reactive species cause oxidative DNA damage, a significant factor in age-related cancer development.
- Oxidative DNA damage can serve as a biomarker for cancer risk and inform dietary modifications.
- Accurate measurement of oxidative DNA damage in relevant tissues is crucial but currently limited.
Purpose of the Study:
- To assess the reliability of measuring oxidative DNA damage as a cancer risk biomarker.
- To investigate whether oxidative DNA damage in blood cells reflects damage in cancer-prone tissues.
- To evaluate the efficacy of dietary interventions in reducing oxidative DNA damage.
Main Methods:
- Review of current literature on oxidative DNA damage measurement techniques.
- Analysis of the common method for assessing DNA damage: 8-hydroxylated guanine (8OHdG).
- Discussion of the limitations and artifactual formation of 8OHdG during analysis.
Main Results:
- There is no consensus on the true levels of 8-hydroxylated guanine (8OHdG) in human DNA.
- 8OHdG may be a minor product of oxidative DNA damage and is prone to artifactual formation.
- Mass spectrometry shows promise for measuring diverse DNA base damage products, but requires improved techniques.
Conclusions:
- Accurate and reliable methods for measuring oxidative DNA damage are urgently needed.
- Dietary intake of fruits and vegetables may decrease oxidative DNA damage in Western populations.
- Ascorbate, vitamin E, and beta-carotene do not appear to reduce oxidative DNA damage.