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      8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis.

      Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews

      Risk Factors, analysis, Reactive Oxygen Species, physiology, Oxidative Stress, Oxidation-Reduction, etiology, epidemiology, Neoplasms, Mutagenesis, Humans, Environmental Exposure, analogs & derivatives, Deoxyguanosine, DNA Damage, Cocarcinogenesis, Carcinogens, Environmental, Biological Markers

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          Abstract

          There is extensive experimental evidence that oxidative damage permanently occurs to lipids of cellular membranes, proteins, and DNA. In nuclear and mitochondrial DNA, 8-hydroxy-2' -deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2' -deoxyguanosine (8-oxodG) is one of the predominant forms of free radical-induced oxidative lesions, and has therefore been widely used as a biomarker for oxidative stress and carcinogenesis. Studies showed that urinary 8-OHdG is a good biomarker for risk assessment of various cancers and degenerative diseases. The most widely used method of quantitative analysis is high-performance liquid chromatography (HPLC) with electrochemical detection (EC), gas chromatography-mass spectrometry (GC-MS), and HPLC tandem mass spectrometry. In order to resolve the methodological problems encountered in measuring quantitatively 8-OHdG, the European Standards Committee for Oxidative DNA Damage was set up in 1997 to resolve the artifactual oxidation problems during the procedures of isolation and purification of oxidative DNA products. The biomarker 8-OHdG or 8-oxodG has been a pivotal marker for measuring the effect of endogenous oxidative damage to DNA and as a factor of initiation and promotion of carcinogenesis. The biomarker has been used to estimate the DNA damage in humans after exposure to cancer-causing agents, such as tobacco smoke, asbestos fibers, heavy metals, and polycyclic aromatic hydrocarbons. In recent years, 8-OHdG has been used widely in many studies not only as a biomarker for the measurement of endogenous oxidative DNA damage but also as a risk factor for many diseases including cancer.

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            Lung Cancer Cardiopulmonary Mortality and Long-term Exposure to Fine Particulate Air Pollution

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              Normal oxidative damage to mitochondrial and nuclear DNA is extensive.

              Oxidative damage to DNA can be caused by excited oxygen species, which are produced by radiation or are by-products of aerobic metabolism. The oxidized base, 8-hydroxydeoxyguanosine (oh8dG), 1 of approximately 20 known radiation damage products, has been assayed in the DNA of rat liver. oh8dG is present at a level of 1 per 130,000 bases in nuclear DNA and 1 per 8000 bases in mtDNA. Mitochondria treated with various prooxidants have an increased level of oh8dG. The high level of oh8dG in mtDNA may be caused by the immense oxygen metabolism, relatively inefficient DNA repair, and the absence of histones in mitochondria. It may be responsible for the observed high mutation rate of mtDNA.
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                Journal
                10.1080/10590500902885684
                19412858

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