DNA repair and the origins of urinary oxidized 2'-deoxyribonucleosides.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractMonitoring oxidative stress in vivo is made easier by the ability to use samples obtained non-invasively, such as urine. The analysis of DNA oxidation, by measurement of oxidized 2'-deoxyribonucleosides in urine, particularly 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), has been reported extensively in the literature in many situations relating to various pathologies, populations and environmental exposures. Understanding the origins of urinary 8-oxodG, other than it simply being a marker of DNA oxidation or its synthetic precursors, is important to being able to effectively interpret differences in baseline urinary 8-oxodG levels between subject groups and changes in excretion. Diet and cell turnover play negligible roles in contributing to urinary 8-oxodG levels, leaving DNA repair as a primary source of this lesion. However, which repair processes contribute, and to what extent, to urinary 8-oxodG is still open to question. The most rational source would be the activity of selected members of the Nudix hydrolase family of enzymes, sanitizing the deoxyribonucleotide pool via the degradation of 8-oxo-7,8-dihydro-2'-deoxyguanosine-5'-triphosphate and 8-oxo-7,8-dihydro-2'-deoxyguanosine-5'-diphosphate, yielding mononucleotide products that can then be dephosphorylated to 8-oxodG and excreted. However, nucleotide excision repair (NER), transcription-coupled repair, nucleotide incision repair (NIR), mismatch repair and various exonuclease activities, such as proofreading function associated with DNA polymerases, can all feasibly generate initial products that could yield 8-oxodG after further metabolism. A recent study implying that a significant proportion of genomic 8-oxodG exists in the context of tandem lesions, refractory to repair by glycosylases, suggests the roles of NER and/or NIR remain to be further examined and defined as a source of 8-oxodG. 8-OxodG has been the primary focus of investigation, but other oxidized 2'-deoxyribonucleosides have been detected in urine, 2'-deoxythymidine glycol and 5-hydroxymethyl-2'-deoxyuridine; the origins of these compounds in urine, however, are presently even more speculative than for 8-oxodG.
CitationMutagenesis 2010, 25 (5):433-442
SponsorsEnvironmental Cancer Risk, Nutrition and Individual Susceptibility, a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘Food Quality and Safety’ (Contract No.513943) to M.D.E., M.S.C.; Fondation pour la Recherche Me´dicale; Electricite´ de France to M.S.
- Measurement and meaning of oxidatively modified DNA lesions in urine.
- Authors: Cooke MS, Olinski R, Loft S, European Standards Committee on Urinary (DNA) Lesion Analysis.
- Issue date: 2008 Jan
- Analysis of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine by liquid chromatography-tandem mass spectrometry.
- Authors: Evans MD, Singh R, Mistry V, Farmer PB, Cooke MS
- Issue date: 2010
- Urinary 8-oxo-2'-deoxyguanosine--source, significance and supplements.
- Authors: Cooke MS, Evans MD, Herbert KE, Lunec J
- Issue date: 2000 May
- Nucleotide excision repair of oxidised genomic DNA is not a source of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine.
- Authors: Evans MD, Mistry V, Singh R, Gackowski D, Różalski R, Siomek-Gorecka A, Phillips DH, Zuo J, Mullenders L, Pines A, Nakabeppu Y, Sakumi K, Sekiguchi M, Tsuzuki T, Bignami M, Oliński R, Cooke MS
- Issue date: 2016 Oct
- Urinary 8-oxo-2'-deoxyguanosine: redox regulation of DNA repair in vivo?
- Authors: Lunec J, Holloway KA, Cooke MS, Faux S, Griffiths HR, Evans MD
- Issue date: 2002 Oct 1