Substantial decrease of urinary 8-oxo-7,8-dihydroguanine, a product of the base excision repair pathway, in DNA glycosylase defective mice

Różalski, Rafał; Siomek, Agnieszka; Gackowski, Daniel; Foksiński, Marek; Gran, Christine; Klungland, Arne

doi:10.1016/j.biocel.2005.01.001

Cited by 43 publications

(22 citation statements)

References 30 publications

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“…Recently, levels of 8-oxoGua were determined in OGG1 À/À mice and compared with a wild-type strain. There was f26% reduction in levels of urinary 8-oxoGua in the deficient strain compared with the wild type, and no significant changes in 8-oxodG were observed (94). This indicates that mouse OGG1 glycosylase is a significant, but by no means unique, source of urinary 8-oxoGua.…”

Section: Sources Of Extracellular Oxidatively Modified Dna Lesionsmentioning

confidence: 85%

Measurement and Meaning of Oxidatively Modified DNA Lesions in Urine

Cooke

Oliński²,

Loft³

2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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206

147

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Background: Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. The noninvasive assessment of such damage, i.e., in urine, and application to large-scale human studies are vital to understanding this role and devising intervention strategies. Methods: We have reviewed the literature to establish the status quo with regard to the methods and meaning of measuring DNA oxidation products in urine. Results: Most of the literature focus upon 8-oxo-7,8-dihydro-2 ¶-deoxyguanosine (8-oxodG), and whereas a large number of these reports concern clinical conditions, there remains (a) lack of consensus between methods, (b) possible contribution from diet and/or cell death, (c) no definitive DNA repair source of urinary 2 ¶-deoxyribonucleoside lesions, and (d) no reference ranges for healthy or diseased individuals. Conclusions: The origin of 8-oxodG is not identified; however, recent cell culture studies suggest that the

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Section: Sources Of Extracellular Oxidatively Modified Dna Lesionsmentioning

confidence: 85%

Measurement and Meaning of Oxidatively Modified DNA Lesions in Urine

Cooke

Oliński²,

Loft³

2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

206

147

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“…In a steady state, the urinary excretion of 8-oxodG and similar products should, in principle, reflect the average rate of oxidative damage in the whole body, whereas the level of lesions in DNA from target cells or surrogate cells, such as leucocytes, should reflect the balance between damage and repair only in these cell types [12]. The relatively limited influence of the repair capacity in steady state was demonstrated by the only 26% lower 8-oxoG excretion and unchanged 8-oxodG excretion in OGG1-knockout mice [32]. So far, the presence of purines or oxidized DNA in the diet has not been shown to contribute to the urinary excretion of 8-oxoG and 8-oxodG [33,34].…”

Section: Type Of Intervention All Interventions Antioxidant Supplemenmentioning

confidence: 98%

Biomarkers of oxidative damage to DNA and repair

Loft

Danielsen

Mikkelsen

et al. 2008

Biochemical Society Transactions

103

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Oxidative-stress-induced damage to DNA includes a multitude of lesions, many of which are mutagenic and have multiple roles in cancer and aging. Many lesions have been characterized by MS-based methods after extraction and digestion of DNA. These preparation steps may cause spurious base oxidation, which is less likely to occur with methods such as the comet assay, which are based on nicking of the DNA strand at modified bases, but offer less specificity. The European Standards Committee on Oxidative DNA Damage has concluded that the true levels of the most widely studied lesion, 8-oxodG (8-oxo-7,8-dihydro-2'-deoxyguanosine), in cellular DNA is between 0.5 and 5 lesions per 10(6) dG bases. Base excision repair of oxidative damage to DNA can be assessed by nicking assays based on oligonucleotides with lesions or the comet assay, by mRNA expression levels or, in the case of, e.g., OGG1 (8-oxoguanine DNA glycosylase 1), responsible for repair of 8-oxodG, by genotyping. Products of repair in DNA or the nucleotide pool, such as 8-oxodG, excreted into the urine can be assessed by MS-based methods and generally reflects the rate of damage. Experimental and population-based studies indicate that many environmental factors, including particulate air pollution, cause oxidative damage to DNA, whereas diets rich in fruit and vegetables or antioxidant supplements may reduce the levels and enhance repair. Urinary excretion of 8-oxodG, genotype and expression of OGG1 have been associated with risk of cancer in cohort settings, whereas altered levels of damage, repair or urinary excretion in case-control settings may be a consequence rather than the cause of the disease.

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“…Recently, an in vitro study showed that 8-oxodG is excreted from cells after exposure to oxidative stress in terms of ionizing radiation (31). 8-Oxoguanine excreted in urine should come from OGG1 mediated repair, although the difference in excretion was only 26% percent between ogg1 Ϫ/Ϫ and ogg1 +/+ mice (74). However, there are many backup repair pathways, including the NEIL1 base excision enzyme (7).…”

Section: Biomarkers Of Dna Damagementioning

confidence: 98%

Oxidative DNA Damage and Human Cancer: Need for Cohort Studies

Loft

Möller

2006

Antioxidants & Redox Signaling

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Research of the role of oxidative DNA damage is well established in experimental carcinogenesis. A large number of human studies on biomarkers of oxidative DNA damage, in particular related to guanine oxidation, have been published. The level of oxidative DNA damage and repair activity can be quite different between tumor and normal tissues; case-control studies have shown increased levels of oxidative DNA damage and decreased repair capacity in leukocytes from cases. Similarly, the urinary biomarkers of oxidative DNA damage may be elevated in patients with cancer. However, such studies are likely to be associated with reverse causality. Case-control studies of genetic polymorphisms in DNA repair enzymes suggest that the common variant Ser326Cys in OGG1 may be a risk factor for lung cancer, whereas a rare variant in OGG1 and germ line mutations in the corresponding mismatch repair gene MYH are risk factors for hereditary colon cancer. Cohort studies are required to provide evidence that a high level of oxidative DNA damage implies a high risk of cancer. However, this represents a real challenge considering the large number of subjects and long followup time required with likely spurious oxidation of DNA during collection, assay and/or storage of samples.

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Substantial decrease of urinary 8-oxo-7,8-dihydroguanine, a product of the base excision repair pathway, in DNA glycosylase defective mice

Cited by 43 publications

References 30 publications

Measurement and Meaning of Oxidatively Modified DNA Lesions in Urine

Measurement and Meaning of Oxidatively Modified DNA Lesions in Urine

Biomarkers of oxidative damage to DNA and repair

Oxidative DNA Damage and Human Cancer: Need for Cohort Studies

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