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Antioxidants & Redox Signaling Apr 20168-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative... (Meta-Analysis)
Meta-Analysis Review
SIGNIFICANCE
8-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative damage of DNA because guanosine is the most oxidized among the DNA nucleobases. In several pathological conditions, high urinary levels of oxidized DNA-derived metabolites have been reported (e.g., cancer, atherosclerosis, hypertension, and diabetes).
RECENT ADVANCES
Even if published studies have shown that DNA damage is significantly associated with the development of atherosclerosis, the exact role of this damage in the onset and progression of this pathology is not fully understood, and the association of oxidative damage to DNA with cardiovascular disease (CVD) still needs to be more extensively investigated. We performed a meta-analysis of the literature to investigate the association among 8-OHdG levels and CVD.
CRITICAL ISSUES
Fourteen studies (810 CVD patients and 1106 controls) were included in the analysis. We found that CVD patients showed higher 8-OHdG levels than controls (SMD: 1.04, 95%CI: 0.61, 1.47, p < 0.001, I(2) = 94%, p < 0.001). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD: 4.43, 95%CI: 1.71, 7.15, p = 0.001) and in blood samples (MD: 1.42, 95%CI: 0.64, 2.21, p = 0.0004). Meta-regression models showed that age, hypertension, and male gender significantly impacted on the difference in 8-OHdG levels among CVD patients and controls.
FUTURE DIRECTIONS
8-OHdG levels are higher in patients with CVD than in controls. However, larger prospective studies are needed to test 8-OHdG as a predictor of CVD.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Deoxyguanosine; Humans; Oxidation-Reduction; Oxidative Stress; Prognosis; Publication Bias; Regression Analysis
PubMed: 26650622
DOI: 10.1089/ars.2015.6508 -
Biochemistry. Biokhimiia Dec 20178-Oxo-7,8-dihydroguanine (8-oxo-G) is a key biomarker of oxidative damage to DNA in cells, and its genotoxicity is well-studied. In recent years, it has been confirmed... (Review)
Review
8-Oxo-7,8-dihydroguanine (8-oxo-G) is a key biomarker of oxidative damage to DNA in cells, and its genotoxicity is well-studied. In recent years, it has been confirmed experimentally that free 8-oxo-G and molecules containing it are not merely inert products of DNA repair or degradation, but they are actively involved in intracellular signaling. In this review, data are systematized indicating that free 8-oxo-G and oxidized (containing 8-oxo-G) extracellular DNA function in the body as mediators of stress signaling and initiate inflammatory and immune responses to maintain homeostasis under the action of external pathogens, whereas exogenous 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo) exhibits pronounced antiinflammatory and antioxidant properties. This review describes known action mechanisms of oxidized guanine and 8-oxo-G-containing molecules. Prospects for their use as a therapeutic target are considered, as well as a pharmaceutical agent for treatment of a wide range of diseases whose pathogenesis is significantly contributed to by inflammation and oxidative stress.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; DNA Damage; DNA Repair; Deoxyguanosine; Guanine; Humans; Inflammation; Oxidative Stress
PubMed: 29523066
DOI: 10.1134/S0006297917130089 -
Disease Markers 2018The objective was to collect the available evidence on oxidative stress marker measurements in periodontal patients, focusing specifically on 8-hydroxy-2'-deoxyguanosine... (Meta-Analysis)
Meta-Analysis Review
The objective was to collect the available evidence on oxidative stress marker measurements in periodontal patients, focusing specifically on 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a salivary marker of periodontal disease, and to perform meta-analyses to calculate differences in concentration compared to healthy persons. A systematic search in PubMed, Cochrane Library, Embase, and Scopus identified 81 articles. Of these, 38 were duplicates. After reading the abstracts of the remaining 43, 42 were selected for full-text assessment. Finally, 17 articles were included in the qualitative synthesis. Those excluded were of low quality, did not answer the research question, or did not meet the inclusion and exclusion criteria. Of the 17 in the qualitative synthesis, 9 were included in the meta-analysis. The 9 studies in the meta-analysis were combined in a random effects model. Their heterogeneity was high ( = 3982.02, < 0.001, = 99.8%). The difference in mean 8-OHdG concentration in saliva between periodontal and healthy subjects was estimated at 2.11 ng/ml (95% CI 1.23-2.98). The different saliva collection methods (stimulated/unstimulated) did not explain the heterogeneity. The 8-OHdG levels in saliva of periodontal patients were almost double to those of healthy patients: 8-OHdG is clearly a powerful periodontal disease marker.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Aggressive Periodontitis; Biomarkers; Deoxyguanosine; Humans; Saliva
PubMed: 29854026
DOI: 10.1155/2018/7916578 -
Advances in Clinical and Experimental... 2017Under homeostatic conditions, an equilibrium state between amounts of free radicals formed and their scavenging is observed. Free radicals are destructive only when... (Review)
Review
Under homeostatic conditions, an equilibrium state between amounts of free radicals formed and their scavenging is observed. Free radicals are destructive only when present in excess. Pathological changes within cells and tissues can result from a persistent excess of free radicals. Living organisms are increasingly exposed to oxidative stress, resulting in oxidative DNA modifications. One such modification is 8-hydroxy-2'-deoxyguanosine (8-OHdG). It is considered a biomarker of oxidative stress and oxidative DNA damage. It has been found both in physiological fluids and in cells. This paper presents methods found in the literature for determining 8-OHdG expression in various kinds of biological material - blood, urine or liver homogenates. Methods for determining the biomarker expression have been grouped into direct and indirect methods, and the various levels of 8-hydroxy-2'-deoxyguanosine that can be determined by the different techniques are presented. The basic pros and cons of the various techniques are also discussed.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; DNA Damage; Deoxyguanosine; Free Radicals; Humans; Oxidative Stress
PubMed: 28397448
DOI: 10.17219/acem/43272 -
The Yale Journal of Biology and Medicine Sep 2020The thyroid is not necessary to sustain life. However, thyroid hormones (TH) strongly affect the human body. Functioning of the thyroid gland affects the reproductive... (Review)
Review
The thyroid is not necessary to sustain life. However, thyroid hormones (TH) strongly affect the human body. Functioning of the thyroid gland affects the reproductive capabilities of women and men, as well as fertilization and maintaining a pregnancy. For the synthesis of TH, hydrogen peroxide (HO) is necessary. From the chemical point of view, TH is a reactive oxygen species (ROS) and serves as an oxidative stress (OS) promoter. HO concentration in the thyroid gland is much higher than in other tissues. Therefore, the thyroid is highly exposed to OS. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) are DNA lesions resulting from ROS action onto guanine moiety. Due to their abundance, they are recognized as biomarkers of OS. As thyroid function is correlated with the level of OS, 8-oxodG and 8-OHdG has been taken under consideration. Studies correlate the oxidative DNA damage with various thyroid diseases (TD) such as Hashimoto's thyroiditis (HT), Graves' disease (GD), and thyroid cancer. Human sexual function and fertility are also affected by OS and TD. Hypothyroidism and hyperthyroidism diagnosed in pregnant women have a negative effect on pregnancy as it may increase the risk of miscarriage or fetus mortality. In the case of TD in the mother, fetal health is also at risk - neurodevelopment and cognitive function of the child may be impaired in its future life. This review presents thyroid function in the context of TD during pregnancy. The authors introduce OS and describe oxidative DNA lesions as a crucial marker of thyroid pathologies.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Child; Deoxyguanosine; Female; Humans; Hydrogen Peroxide; Male; Pregnancy; Reactive Oxygen Species; Thyroid Diseases
PubMed: 33005115
DOI: No ID Found -
The Science of the Total Environment Apr 2023Selenium is an element present in trace amounts and different chemical forms. It may exert both beneficial and adverse effects on cellular redox status and on the...
Selenium is an element present in trace amounts and different chemical forms. It may exert both beneficial and adverse effects on cellular redox status and on the generation of reactive oxygen species. 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine, and a sensitive biomarker of oxidative stress and genotoxicity. The present study assessed the extent to which selenium status was associated with urinary 8-oxodG concentrations in a Northern Italian population. We recruited healthy, non-smoking blood donors living in the Reggio Emilia province during 2017-2019. We measured urinary 8-oxodG concentrations and used restricted cubic spline regression analyses to investigate the association between selenium status (estimated using food frequency questionnaires, urinary concentrations, and serum concentrations of selenium and selenium species) and 8-oxodG/g creatinine. Among 137 participants aged 30-60 years, median urinary selenium and 8-oxodG concentrations were 22.02 μg/L and 3.21 μg/g creatinine, respectively. Serum samples and selenium speciation analyses were available for 104 participants. Median total serum selenium levels and dietary intake were 116.5 μg/L and 78.7 μg/day, respectively. In spline regression analysis, there was little association between dietary, serum, or urinary selenium with 8-oxodG concentrations. In sex-specific analyses, urinary selenium showed a positive association with the endpoint among males. For single selenium species, we observed positive associations with urinary 8-oxodG for serum organic selenium species, and negative associations for inorganic selenium forms. In the most adjusted analysis, urinary 8-oxodG concentrations showed a strong positive association with selenomethione-bound selenium (Se-Met) and a negative association with inorganic tetravalent selenium, selenite. In sex-specific analyses, these associations were considerably stronger in males than in females. Overall, study findings indicate that selenium species exhibited very different patterns of associations with the biomarker of oxidative stress, and that these associations also depended on sex. Background exposure to Se-Met appears to be strongly and positively associated with oxidative stress.
Topics: Male; Female; Humans; 8-Hydroxy-2'-Deoxyguanosine; Deoxyguanosine; Selenium; Creatinine; Oxidative Stress; Biomarkers
PubMed: 36702271
DOI: 10.1016/j.scitotenv.2023.161584 -
Journal of Chromatography. B,... Jun 20184-Aminobiphenyl (4-ABP) which is primarily formed during tobacco combustion and overheated meat is a major carcinogen responsible for various cancers. Its adducted form,... (Review)
Review
4-Aminobiphenyl (4-ABP) which is primarily formed during tobacco combustion and overheated meat is a major carcinogen responsible for various cancers. Its adducted form, N-deoxyguanosine-C8-4-aminobiphenyl (dG-C8-4-ABP), has long been employed as a biomarker for assessment of the risk for cancer. In this review, the metabolism and carcinogenisity of 4-ABP will be discussed, followed by a discussion of the current common approaches of analyzing dG-C8-4-ABP. The major part of this review will be on the history and recent development of key methods for detection and quantitation of dG-C8-4-ABP in complex biological samples and their biological applications, from the traditional P-postlabelling and immunoassay methods to modern liquid chromatography-mass spectrometry (LC-MS) with the latter as the focus. Many vital biological discoveries based on dG-C8-4-ABP have been published by using the nanoLC-MS with column switching platform in our laboratory, which has also been adopted and further improved by many other researchers. We hope this review can provide a perspective of the challenges that had to be addressed in reaching our present goals and possibly bring new ideas for those who are still working on the frontline of DNA adducts area.
Topics: Aminobiphenyl Compounds; Animals; Biomarkers; Chromatography, Liquid; Deoxyguanosine; Humans; Limit of Detection; Linear Models; Mass Spectrometry; Mice; Microfluidic Analytical Techniques; Occupational Exposure; Tissue Distribution
PubMed: 29709872
DOI: 10.1016/j.jchromb.2018.04.041 -
Revista Da Associacao Medica Brasileira... Nov 2021Reactive oxygen species and oxygen free radicals cause oxidative damage to lipids, proteins, and cell DNA in the cell membrane. Although many DNA products are produced...
OBJECTIVE
Reactive oxygen species and oxygen free radicals cause oxidative damage to lipids, proteins, and cell DNA in the cell membrane. Although many DNA products are produced during oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the most common one, since it can be produced in in vivo environment. In recent years, diving has been done quite frequently for business and sports purposes all over the world. Increased environmental pressure in diving leads to hyperoxia and causes oxidative stress.
METHODS
The acute effects of diving on DNA damage were evaluated by comparing 8-hydroxy-2'-deoxyguanosine values of 15 professional diver groups before and after diving. In addition to the demographic characteristics, the serum 8-hydroxy-2'-deoxyguanosine levels of these 15 divers were compared with the control group consisting of nondiving medical students to examine the chronic effect of diving on DNA damage.
RESULTS
After deep dive, the amount of 8-hydroxy-2'-deoxyguanosine increased significantly in the diver group and acute DNA damage was observed (T1: 38.86±4.7; T2: 51.77±4.53; p<0.05). In the control group, the amount of 8-hydroxy-2'-deoxyguanosine was insignificant (C1: 47.48±3.73; T1: 38.86±4.7; p>0.05).
CONCLUSIONS
It was found that air dives caused an increase in serum 8-hydroxy-2'-deoxyguanosine levels, leading to acute oxidative stress and aging. However, there is no chronic side effect, according to the study of samples taken from the control group. This was thought to be due to the relative sedentary life of the control group. The duration of the effect or the ability to return to normal values should be investigated with further studies planned with large populations.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; DNA Damage; Deoxyguanosine; Humans; Oxidative Stress; Reactive Oxygen Species
PubMed: 34909901
DOI: 10.1590/1806-9282.20210748 -
International Journal of Molecular... Jan 2023The guanine base in nucleic acids is, among the other bases, the most susceptible to being converted into 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) when exposed to... (Review)
Review
The guanine base in nucleic acids is, among the other bases, the most susceptible to being converted into 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) when exposed to reactive oxygen species. In double-helix DNA, 8-oxodG can pair with adenine; hence, it may cause a G > T (C > A) mutation; it is frequently referred to as a form of DNA damage and promptly corrected by DNA repair mechanisms. Moreover, 8-oxodG has recently been redefined as an epigenetic factor that impacts transcriptional regulatory elements and other epigenetic modifications. It has been proposed that 8-oxodG exerts epigenetic control through interplay with the G-quadruplex (G4), a non-canonical DNA structure, in transcription regulatory regions. In this review, we focused on the epigenetic roles of 8-oxodG and the G4 and explored their interplay at the genomic level.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Deoxyguanosine; DNA Damage; DNA Repair; DNA
PubMed: 36768357
DOI: 10.3390/ijms24032031 -
The Journal of Biological Chemistry Apr 2020Exogenous and endogenous chemicals can react with DNA to produce DNA lesions that may block DNA replication. Not much is known about the roles of polymerase (Pol) ν and...
Exogenous and endogenous chemicals can react with DNA to produce DNA lesions that may block DNA replication. Not much is known about the roles of polymerase (Pol) ν and Pol θ in translesion synthesis (TLS) in cells. Here we examined the functions of these two polymerases in bypassing major-groove -alkyl-2'-deoxyguanosine (-alkyl-dG) and minor-groove -alkyl-dG lesions in human cells, where the alkyl groups are ethyl, -butyl (Bu), and, for -alkyl-dG, pyridyloxobutyl. We found that Pol ν and Pol θ promote TLS across major-groove -alkyl-dG lesions. -alkyl-dG lesions mainly induced G→A mutations that were modulated by the two TLS polymerases and the structures of the alkyl groups. Simultaneous ablation of Pol ν and Pol θ resulted in diminished mutation frequencies for all three -alkyl-dG lesions. Depletion of Pol ν alone reduced mutations only for -Bu-dG, and sole loss of Pol θ attenuated the mutation rates for -Bu-dG and -pyridyloxobutyl-dG. Replication across the two -alkyl-dG lesions was error-free, and Pol ν and Pol θ were dispensable for their replicative bypass. Together, our results provide critical knowledge about the involvement of Pol ν and Pol θ in bypassing alkylated guanine lesions in human cells.
Topics: Alkylation; Chromatography, High Pressure Liquid; DNA Repair; DNA-Directed DNA Polymerase; Deoxyguanosine; HEK293 Cells; Humans; Mutagenesis; Tandem Mass Spectrometry; DNA Polymerase theta
PubMed: 32098870
DOI: 10.1074/jbc.RA120.012830