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8-Hydroxydeoxyguanosine (8-OHdG) is a crucial biomarker for measuring oxidative stress and DNA damage.  

Formed when reactive oxygen species (ROS) oxidize guanine in DNA, 8-OHdG reflects the extent of oxidative damage, making it essential for understanding various health conditions. 

8-OHdG also directly contributes to DNA damage, leading to mutations and genomic instability.  It also acts as a signaling molecule, triggering pathways involved in DNA repair, cell cycle regulation, and apoptosis. 

Studies show that breast cancer patients have significantly higher urinary 8-OHdG levels than healthy controls, with levels decreasing as cancer progresses.  This suggests a complex relationship between oxidative stress and breast cancer development. 

Measuring 8-OHdG in urine, blood, and tissues, but especially in urine, helps assess oxidative stress in diseases like cardiovascular diseases, neurodegenerative disorders, and cancer. 

Factors such as age, gender, lifestyle, environmental exposures, and genetic variations influence 8-OHdG levels, affecting its reliability as a biomarker. 

Definition and Biological Significance of 8-OHdG

Understanding the biological significance of 8-OHdG is crucial for grasping its role as a biomarker and its implications for health and disease. 

Formation of 8-OHdG  

8-OHdG is generated through the oxidation of guanine, one of the four nucleotide bases in DNA, by reactive oxygen species (ROS) such as hydroxyl radicals and singlet oxygen.  This oxidative modification results in the formation of a hydroxyl group at the eighth position of the guanine base, leading to the production of 8-OHdG.  [5.] 

The occurrence of 8-OHdG in DNA reflects the extent of oxidative stress experienced by cells and tissues, making it a valuable indicator of oxidative damage to DNA.

8-OHdG’s Role in DNA Damage

Beyond its role as a marker of DNA damage, 8-OHdG is directly involved in DNA damage. 

Studies have shown that 8-OHdG can interfere with DNA replication and transcription, leading to mutations, genomic instability, and alterations in gene expression.  [9.]

Additionally, 8-OHdG can serve as a signaling molecule, activating pathways involved in DNA repair, cell cycle regulation, and apoptosis in response to oxidative stress.  [14.]  

The dysregulation of these processes due to aberrant levels of 8-OHdG can contribute to the development and progression of disease.

8-OHdG in Breast Cancer  [10.] 

One study investigated the role of reactive oxygen species (ROS) in breast cancer by measuring urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in breast cancer patients and assessing their association with cancer development.  

Sixty patients with malignant breast tumors were compared to 60 age-matched controls.  Results showed significantly higher 8-OHdG levels in breast cancer patients, even after adjusting for smoking, coffee consumption, and oral contraceptive use. 

Interestingly, 8-OHdG levels decreased as cancer progressed through its stages.  

Multiple regression and logistic models confirmed a significant correlation between urinary 8-OHdG levels and breast cancer development, independent of CYP1A1, CYP1M1, or NAT2 polymorphisms. 

The study concluded that while oxidative stress contributes to DNA damage in breast carcinoma, further evaluation of gene polymorphisms is also needed to understand their role in breast cancer.

8-OHdG Clinical Significance As A Biomarker

8-OHdG levels can be measured in various biological samples, including urine, blood, and tissues, and are used as a biomarker of oxidative stress and DNA damage associated with various diseases. 

Elevated levels of 8-OHdG have been associated with various pathological conditions such as cardiovascular diseases, neurodegenerative disorders, cancer, and aging.  [1., 6., 15., 17.]    Elevated levels have also been associated with increased exposure to environmental toxins.  [17.] 

Studies have shown that urinary 8-OHdG is a good biomarker for risk assessment of various cancers and degenerative diseases.  [8.]  However, as emphasized in the literature, collecting spot morning urine samples is recommended to facilitate comparison between studies.  [8.] 

Factors Affecting 8-OHdG Levels  [5., 11., 12., 13.]

Various factors can influence 8-OHdG levels, impacting its reliability as a biomarker of oxidative DNA damage and disease risk. 

Age and gender are significant determinants, with studies showing increased 8-OHdG levels with advancing age and higher levels in males compared to females, potentially due to hormonal differences and/or lifestyle factors. 

Lifestyle factors such as diet, exercise, smoking, and alcohol consumption can  impact oxidative stress and 8-OHdG levels.  Environmental exposures to pollutants, toxins, and radiation also contribute to oxidative stress and DNA damage, leading to elevated 8-OHdG levels in exposed populations.

Genetic variations in genes encoding antioxidant enzymes, DNA repair proteins, and other factors involved in oxidative stress responses can influence individual susceptibility to oxidative DNA damage and affect 8-OHdG levels.

Additionally, gene-environment interactions may modulate 8-OHdG levels, highlighting the importance of considering these factors in oxidative stress research .

Lab Testing for 8-OHdG

Laboratory testing for 8-OHdG is essential for quantifying oxidative DNA damage and assessing its implications for health and disease.  As mentioned above, various methods are available to assess 8-OHdG levels, although urinary 8-OHdG as a first-morning void sample may be the easiest and most clinically relevant option.  [8.]

Sample Collection and Handling

For urine samples, it is essential to collect first-morning voids or 24-hour urine samples to minimize variations in urinary excretion rates.  

Blood samples are collected via venipuncture.  

Interpretation of Test Results

Interpreting test results for 8-OHdG requires consideration of various factors, including age, sex, smoking status, and underlying health conditions.  [19.] 

It is essential to interpret 8-OHdG levels in the context of other biomarkers of oxidative stress and DNA damage, as well as clinical symptoms and diagnostic findings, to accurately assess an individual's risk profile and guide appropriate interventions.

Optimal Levels of 8-OHdG Levels

Because 8-OHdG is a biomarker of DNA damage, lower levels are considered optimal.  

It is essential to consult the laboratory company used for interpretation of their findings; one such company reports a reference range of the following for first morning 8-OHdG levels:  [16.] 

0-5.2 ng/mg

Low Levels of 8-OHdG

Low levels of 8-OHdG are considered optimal.

High Levels of 8-OHdG

Elevated levels of 8-OHdG signify increased DNA damage and warrant further assessment for sources of cellular damage including inflammation or toxins.  Additional testing for antioxidant capacity and other biomarkers may be warranted.  

8-OHdG Related Biomarkers to Test


8-Isoprostane, also known as F2-isoprostane, is a prostaglandin-like compound formed by the non-enzymatic oxidation of arachidonic acid. It serves as a reliable marker of lipid peroxidation, reflecting oxidative damage to cell membranes and lipids. [18.] 

Like 8-OHdG, 8-isoprostane levels increase in response to oxidative stress and have been implicated in the pathogenesis of various diseases including cardiovascular disease and inflammatory conditions.  [4.]

Measuring both 8-OHdG and 8-isoprostane provides complementary information on oxidative damage to DNA and lipids, offering a more comprehensive assessment of oxidative stress status.

Protein Carbonyls

Protein carbonyls are formed through the oxidation of amino acid side chains, primarily lysine, arginine, proline, and threonine residues, by reactive oxygen species.  Elevated levels of protein carbonyls indicate oxidative damage to proteins, leading to impaired cellular function and increased susceptibility to proteolytic degradation.  [3.]

Protein carbonylation has been implicated in the pathogenesis of aging-related diseases, neurodegenerative disorders, and metabolic conditions such as diabetes.  [2., 3., 7.] 

Assessing protein carbonyl levels alongside 8-OHdG provides insight into oxidative damage to cellular macromolecules and the overall burden of oxidative stress on cellular function and homeostasis.

Total Antioxidant Capacity  [1.] 

In addition to measuring markers of oxidative damage, assessing total antioxidant capacity (TAC) provides insight into the body's ability to counteract oxidative stress and maintain redox balance. 

TAC represents the cumulative antioxidant capacity of endogenous antioxidants such as glutathione, superoxide dismutase, catalase, and exogenous antioxidants obtained from dietary sources. 

A balance between oxidative damage and antioxidant defense mechanisms is crucial for maintaining cellular integrity and preventing oxidative stress-related diseases.  

Evaluating TAC alongside 8-OHdG and other oxidative stress biomarkers offers a more holistic view of oxidative stress status and disease risk, guiding targeted interventions to restore redox balance and mitigate disease progression.

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8-Hydroxy-2-deoxyguanosine, often abbreviated as 8-OHdG, is a compound that occurs naturally in your body. It's a byproduct of a process called oxidative stress, which happens when your body uses oxygen to create energy. Think of it like the exhaust that comes out of a car after it burns gasoline. 8-OHdG is particularly interesting because it's linked to your DNA - the blueprint of life that's found in every cell of your body. When oxidative stress occurs, 8-OHdG can be formed directly in your DNA. Scientists often measure the levels of 8-OHdG to understand how much oxidative stress a person's body is undergoing. In a nutshell, 8-OHdG is like a biological smoke detector. It doesn't cause the fire, but its presence can tell us that something is burning.
If Your Levels Are High
High levels of 8-Hydroxy-2-deoxyguanosine, or 8-OHdG, in your body could indicate that your body is experiencing a high level of oxidative stress. Oxidative stress is like a car engine running hot; it's a natural process where your body uses oxygen to produce energy, but it can also produce 'exhaust' in the form of 8-OHdG. This compound is directly linked to your DNA, the blueprint of life in every cell. So, if you have high levels of 8-OHdG, it's like a smoke alarm going off, signaling that your body's 'engine' is running hot. This could be due to a variety of factors, such as exposure to environmental toxins, certain medications like chemotherapy drugs, or health conditions like diabetes or heart disease. It's not the 8-OHdG causing the problem, but its presence can indicate that something else is putting stress on your body.
Symptoms of High Levels
Symptoms of high levels of 8-Hydroxy-2-deoxyguanosine are not specific, as it is a marker of oxidative stress rather than a disease itself. However, it could be associated with symptoms related to the underlying cause of the oxidative stress, such as fatigue, weakness, or other symptoms related to conditions like diabetes or heart disease.
If Your Levels are Low
8-OHdG is a substance that your body makes when it uses oxygen to produce energy, similar to how a car produces exhaust when it burns fuel. This substance is connected to your DNA, the instruction manual for all the cells in your body. When your body is under stress from things like poor diet, lack of sleep, or certain medications like chemotherapy drugs, it can produce more 8-OHdG. Scientists often check how much 8-OHdG is in your body to see how much stress your body is under. If your levels are low, it could mean that your body isn't under a lot of stress, or that it's effectively managing the stress it's under.
Symptoms of Low Levels
Symptoms of low levels of 8-Hydroxy-2-deoxyguanosine may not be easily noticeable as this substance is more of an indicator of oxidative stress rather than a cause of specific symptoms.
See References

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[2.] Almogbel E, Rasheed N. Protein Mediated Oxidative Stress in Patients with Diabetes and its Associated Neuropathy: Correlation with Protein Carbonylation and Disease Activity Markers. J Clin Diagn Res. 2017 Feb;11(2):BC21-BC25. doi: 10.7860/JCDR/2017/23789.9417. Epub 2017 Feb 1. PMID: 28384853; PMCID: PMC5376809.

[3.] Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as 

biomarkers of oxidative stress. Clin Chim Acta. 2003 Mar;329(1-2):23-38. doi: 10.1016/s0009-8981(03)00003-2. PMID: 12589963.

[4.] de Faria, A.P., Modolo, R., Moreno, H. (2016). Plasma 8-Isoprostane as a Biomarker and Applications to Cardiovascular Disease. In: Patel, V., Preedy, V. (eds) Biomarkers in Cardiovascular Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht.

[5.] Di Minno A, Turnu L, Porro B, Squellerio I, Cavalca V, Tremoli E, Di Minno MN. 8-Hydroxy-2-Deoxyguanosine Levels and Cardiovascular Disease: A Systematic Review and Meta-Analysis of the Literature. Antioxid Redox Signal. 2016 Apr 1;24(10):548-55. doi: 10.1089/ars.2015.6508. PMID: 26650622; PMCID: PMC4827317.

[6.] Gmitterová K, Heinemann U, Gawinecka J, Varges D, Ciesielczyk B, Valkovic P, Benetin J, Zerr I. 8-OHdG in cerebrospinal fluid as a marker of oxidative stress in various neurodegenerative diseases. Neurodegener Dis. 2009;6(5-6):263-9. doi: 10.1159/000237221. Epub 2009 Dec 3. PMID: 19955696.

[7.] Gonos ES, Kapetanou M, Sereikaite J, Bartosz G, Naparło K, Grzesik M, Sadowska-Bartosz I. Origin and pathophysiology of protein carbonylation, nitration and chlorination in age-related brain diseases and aging. Aging (Albany NY). 2018 May 17;10(5):868-901. doi: 10.18632/aging.101450. PMID: 29779015; PMCID: PMC5990388.

[8.] Graille M, Wild P, Sauvain JJ, Hemmendinger M, Guseva Canu I, Hopf NB. Urinary 8-OHdG as a Biomarker for Oxidative Stress: A Systematic Literature Review and Meta-Analysis. Int J Mol Sci. 2020 May 26;21(11):3743. doi: 10.3390/ijms21113743. PMID: 32466448; PMCID: PMC7313038.

[9.] Hahm, J.Y., Park, J., Jang, ES. et al. 8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification. Exp Mol Med 54, 1626–1642 (2022).

[10.] Hsien Wen Kuo, Sze Yuan Chou, Tsung Wen Hu, Fang Yang Wu, Da Jen Chen. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and genetic polymorphisms in breast cancer patients. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2007;631(1):62-68. doi:

[11.] Loft S, Vistisen K, Ewertz M, Tjønneland A, Overvad K, Poulsen HE. Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index. Carcinogenesis. 1992 Dec;13(12):2241-7. doi: 10.1093/carcin/13.12.2241. PMID: 1473230.

[12.] Mao Z, Gray ALH, Thyagarajan B, Bostick RM. Antioxidant enzyme and DNA base repair genetic risk scores' associations with systemic oxidative stress biomarker in pooled cross-sectional studies. Front Aging. 2023 Apr 21;4:1000166. doi: 10.3389/fragi.2023.1000166. PMID: 37152862; PMCID: PMC10161255.

[13.] Møller P, Folkmann JK, Forchhammer L, Bräuner EV, Danielsen PH, Risom L, Loft S. Air pollution, oxidative damage to DNA, and carcinogenesis. Cancer Lett. 2008 Jul 18;266(1):84-97. doi: 10.1016/j.canlet.2008.02.030. Epub 2008 Mar 25. PMID: 18367322.

[14.] Poetsch AR. The genomics of oxidative DNA damage, repair, and resulting mutagenesis. Comput Struct Biotechnol J. 2020 Jan 7;18:207-219. doi: 10.1016/j.csbj.2019.12.013. PMID: 31993111; PMCID: PMC6974700.

[15.] Rall LC, Ronenn Roubenoff, Simin Nikbin Meydani, Sung Nim Han, Mohsen Meydani. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) as a marker of oxidative stress in rheumatoid arthritis and aging: effect of progressive resistance training. The Journal of Nutritional Biochemistry. 2000;11(11-12):581-584. doi:

‌[16.] Rupa Health.  1.DUTCH OATs Sample Report.pdf. Google Docs. Accessed May 14, 2024.

[17.] VALAVANIDIS, A., VLACHOGIANNI, T., & FIOTAKIS, C. (2009). 8-hydroxy-2′ -deoxyguanosine (8-OHdG): A Critical Biomarker of Oxidative Stress and Carcinogenesis. Journal of Environmental Science and Health, Part C, 27(2), 120–139.

[18.] van 't Erve TJ, Kadiiska MB, London SJ, Mason RP. Classifying oxidative stress by F2-isoprostane levels across human diseases: A meta-analysis. Redox Biol. 2017 Aug;12:582-599. doi: 10.1016/j.redox.2017.03.024. Epub 2017 Mar 28. PMID: 28391180; PMCID: PMC5384299.

[19.] Watanabe S, Li YS, Kawasaki Y, Ootsuyama Y, Kawai K. Health examination results and work environment factors affecting urinary 8-hydroxy-2'-deoxyguanosine levels. J Occup Health. 2021 Jan;63(1):e12210. doi: 10.1002/1348-9585.12210. Erratum in: J Occup Health. 2021 Jan;63(1):e12230. PMID: 33689200; PMCID: PMC7945954.

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