8-Hydroxy-2-deoxyguanosine

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

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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