Sources of extracellular, oxidatively-modified DNA lesions: implications for their measurement in urine.

2.50
Hdl Handle:
http://hdl.handle.net/10146/114934
Title:
Sources of extracellular, oxidatively-modified DNA lesions: implications for their measurement in urine.
Authors:
Cooke, Marcus S.; Henderson, Paul T.; Evans, Mark D.
Abstract:
There is a robust mechanistic basis for the role of oxidation damage to DNA in the aetiology of various major diseases (cardiovascular, neurodegenerative, cancer). Robust, validated biomarkers are needed to measure oxidative damage in the context of molecular epidemiology, to clarify risks associated with oxidative stress, to improve our understanding of its role in health and disease and to test intervention strategies to ameliorate it. Of the urinary biomarkers for DNA oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most studied. However, there are a number of factors which hamper our complete understanding of what meausrement of this lesion in urine actually represents. DNA repair is thought to be a major contributor to urinary 8-oxodG levels, although the precise pathway(s) has not been proven, plus possible contribution from cell turnover and diet are possible confounders. Most recently, evidence has arisen which suggests that nucleotide salvage of 8-oxodG and 8-oxoGua can contribute substantially to 8-oxoG levels in DNA and RNA, at least in rapidly dividing cells. This new observation may add an further confounder to the conclusion that 8-oxoGua or 8-oxodG, and its nucleobase equivalent 8-oxoguanine, concentrations in urine are simply a consequence of DNA repair. Further studies are required to define the relative contributions of metabolism, disease and diet to oxidised nucleic acids and their metabolites in urine in order to develop urinalyis as a better tool for understanding human disease.
Citation:
J Clin Biochem Nutr 2009, 45 (3):255-270
Journal:
Journal of Clinical Biochemistry and Nutrition
Issue Date:
Nov-2009
URI:
http://hdl.handle.net/10146/114934
DOI:
10.3164/jcbn.SR09-41
PubMed ID:
19902015
Additional Links:
http://www.jstage.jst.go.jp/article/jcbn/45/3/45_255/_article; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771246/?tool=pubmed
Type:
Article
Language:
en
ISSN:
1880-5086
Sponsors:
MSC and MDE are partners of ECNIS (Environmental 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). PTH was supported by National Institutes of Health Grants RR13461, CA93373, the California Breast Cancer Research Program Grant 9KB-0179 and the Knapp Family Fund.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorCooke, Marcus S.en
dc.contributor.authorHenderson, Paul T.en
dc.contributor.authorEvans, Mark D.en
dc.date.accessioned2010-11-08T11:15:22Z-
dc.date.available2010-11-08T11:15:22Z-
dc.date.issued2009-11-
dc.identifier.citationJ Clin Biochem Nutr 2009, 45 (3):255-270en
dc.identifier.issn1880-5086-
dc.identifier.pmid19902015-
dc.identifier.doi10.3164/jcbn.SR09-41-
dc.identifier.urihttp://hdl.handle.net/10146/114934-
dc.description.abstractThere is a robust mechanistic basis for the role of oxidation damage to DNA in the aetiology of various major diseases (cardiovascular, neurodegenerative, cancer). Robust, validated biomarkers are needed to measure oxidative damage in the context of molecular epidemiology, to clarify risks associated with oxidative stress, to improve our understanding of its role in health and disease and to test intervention strategies to ameliorate it. Of the urinary biomarkers for DNA oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most studied. However, there are a number of factors which hamper our complete understanding of what meausrement of this lesion in urine actually represents. DNA repair is thought to be a major contributor to urinary 8-oxodG levels, although the precise pathway(s) has not been proven, plus possible contribution from cell turnover and diet are possible confounders. Most recently, evidence has arisen which suggests that nucleotide salvage of 8-oxodG and 8-oxoGua can contribute substantially to 8-oxoG levels in DNA and RNA, at least in rapidly dividing cells. This new observation may add an further confounder to the conclusion that 8-oxoGua or 8-oxodG, and its nucleobase equivalent 8-oxoguanine, concentrations in urine are simply a consequence of DNA repair. Further studies are required to define the relative contributions of metabolism, disease and diet to oxidised nucleic acids and their metabolites in urine in order to develop urinalyis as a better tool for understanding human disease.en
dc.description.sponsorshipMSC and MDE are partners of ECNIS (Environmental 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). PTH was supported by National Institutes of Health Grants RR13461, CA93373, the California Breast Cancer Research Program Grant 9KB-0179 and the Knapp Family Fund.en
dc.language.isoenen
dc.relation.urlhttp://www.jstage.jst.go.jp/article/jcbn/45/3/45_255/_articleen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771246/?tool=pubmeden
dc.subjectDNA Damageen
dc.subjectOxidative Stressen
dc.subjectDNA Repairen
dc.subjectBiomarkersen
dc.subjectUrineen
dc.subjectCell Deathen
dc.titleSources of extracellular, oxidatively-modified DNA lesions: implications for their measurement in urine.en
dc.typeArticleen
dc.identifier.journalJournal of Clinical Biochemistry and Nutritionen

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