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

Our plain-English summary of 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis, by A. Valavanidis, T. Vlachogianni, C. Fiotakis (Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews, 2009).

The study

• Authors: A. Valavanidis, T. Vlachogianni, C. Fiotakis
• Journal: Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews
• Published: 2009;27(2):120-39
• Type of article: Review
• Cited by: 1,539 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This article was a narrative review of research on 8-hydroxy-2'-deoxyguanosine (8-OHdG, also called 8-oxodG), a form of DNA damage caused by oxygen free radicals that can be measured in urine, organs and white blood cells. The authors described how the marker was discovered in 1984, how it is measured, and how differences between laboratory methods had produced inconsistent results. They summarized earlier studies that used the marker after exposure to tobacco smoke, asbestos, diesel exhaust, air pollution, metals and other carcinogens. For asbestos, the review cited studies reporting three things. Asbestos fibers produced hydroxyl radicals and oxidative DNA damage in cell-free systems and cultured cells. 8-OHdG formed in white blood cells of highly exposed workers. High urinary levels in exposed workers correlated positively with duration of exposure. Separately, in its discussion of tobacco smoking, the review cited a cohort of 53,689 men and women aged 50–64. In that cohort, urinary 8-oxodG was higher in current smokers, and the lung cancer incidence rate ratio was 0.99 (95% confidence interval 0.80–1.22) per doubling of 8-oxodG excretion. The authors concluded that 8-OHdG has been established as a biomarker for carcinogenesis, aging and degenerative diseases.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published literature; no new data were collected
• Who was studied: No study population of its own. The authors reviewed published research on 8-OHdG/8-oxodG, with references up to 2008. They noted the size of that literature as found in a Google Scholar search at the end of 2008.
• Exposure: Exposures discussed in the reviewed studies included tobacco smoke, asbestos fibers, heavy metals, polycyclic aromatic hydrocarbons, diesel exhaust and particulate air pollution, benzene, styrene and inorganic arsenic.
• Main results:
  • Studies cited by the review (cell-free systems and cultured cells) reported that asbestos fibers produced hydroxyl radicals and caused oxidative DNA damage.
  • Studies cited by the review reported 8-OHdG formation in the DNA of white blood cells of workers highly exposed to asbestos at the workplace.
  • A study cited by the review found high urinary levels in asbestos-exposed workers, which correlated positively with duration of exposure.
  • The review discussed a cohort in its section on tobacco smoking; it was not described as asbestos-exposed. The cohort comprised 53,689 men and women aged 50–64, followed for 3–7 years, including 260 lung cancer cases. Urinary 8-oxodG excretion was higher in current smokers. The lung cancer incidence rate ratio was 0.99 (95% confidence interval 0.80–1.22) per doubling of 8-oxodG excretion.
  • The review reported that the European Standards Committee on Oxidative Damage, set up in 1997 with 27 laboratories, found the LC-MS-MS method as reliable, sensitive and precise as the best HPLC procedures.
  • The review reported that the most recent estimates of steady-state 8-oxodG levels in human lymphocyte DNA were 0.2–2.0 lesions per 10^6 nucleobases. The text prints this as "106", where a superscript was lost.
• The authors' conclusion: The authors concluded that 8-OHdG, first reported by Kasai and Nishimura in 1984, has been established as a biomarker not only for carcinogenesis but also for aging and degenerative diseases.
• Limitations the authors state:
  • The authors noted that differences in laboratory methods had led to inconsistent results, with background levels of 8-OHdG in human DNA sometimes exaggerated by up to two or three orders of magnitude.

Topics

Medical terms in this study, explained in our Lexicon: 8-OHdG, Biomarker, Oxidative Stress, Carcinogenesis.

Related studies

• 8-Hydroxy-2'-deoxyguanosine as a marker of oxidative DNA damage related to occupational and environmental exposures — A. Pilger, H.W. Rüdiger (2006)
• Association between 8-hydroxy-2'-deoxyguanosine levels in DNA of workers highly exposed to asbestos and their clinical data, occupational and non-occupational confounding factors, and cancer — B. Marczynski, T. Kraus, et al. (2000)
• Detection of 8-oxo-2'-deoxyguanosine, a marker of oxidative DNA damage, in culture medium from human mesothelial cells exposed to crocidolite asbestos — Q. Chen, J. Marsh, et al. (1996)
• Determination of carcinogenic potential of mineral fibers by 8-hydroxydeoxyguanosine as a marker of oxidative DNA damage in mammalian cells — N. Murata-Kamiya, T. Tsutsui, et al. (1997)
• Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos — H. Fung, Y.W. Kow, et al. (1997)
• Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles — A. Valavanidis, T. Vlachogianni, et al. (2009)

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