Measurement and meaning of oxidatively modified DNA lesions in urine.

2.50
HDL Handle:
http://hdl.handle.net/10146/31874
Title:
Measurement and meaning of oxidatively modified DNA lesions in urine.
Authors:
Cooke, Marcus S.; Olinski, Ryszard; Loft, Steffen
Abstract:
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 action of Nudix hydrolase(s) on oxidative modification of the nucleotide pool is a likely candidate for the 8-oxodG found in urine and, potentially, of other oxidized 2'-deoxyribonucleoside lesions. Literature reports suggest that diet and cell death have minimal, if any, influence upon urinary levels of 8-oxodG and 8-oxo-7,8-dihydroguanine, although this should be assessed on a lesion-by-lesion basis. Broadly speaking, there is consensus between chromatographic techniques; however, ELISA approaches continue to overestimate 8-oxodG levels and is not sufficiently specific for accurate quantification. With increasing numbers of lesions being studied, it is vital that these fundamental issues are addressed. We report the formation of the European Standards Committee on Urinary (DNA) Lesion Analysis whose primary goal is to achieve consensus between methods and establish reference ranges in health and disease.
Citation:
Cancer Epidemiol. Biomarkers Prev. 2008, 17 (1):3-14
Journal:
Cancer Epidemiology, Biomarkers & Prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Issue Date:
Jan-2008
URI:
http://hdl.handle.net/10146/31874
DOI:
10.1158/1055-9965.EPI-07-0751
PubMed ID:
18199707
Additional Links:
http://cebp.aacrjournals.org/cgi/content/full/17/1/3
Type:
Article
Language:
en
ISSN:
1055-9965
Appears in Collections:
Articles

Full metadata record

DC FieldValueLanguage
dc.contributor.authorCooke, Marcus S.-
dc.contributor.authorOlinski, Ryszard-
dc.contributor.authorLoft, Steffen-
dc.date.accessioned2008-07-14T11:22:41Z-
dc.date.available2008-07-14T11:22:41Z-
dc.date.issued2008-01-
dc.identifier.citationCancer Epidemiol. Biomarkers Prev. 2008, 17 (1):3-14en
dc.identifier.issn1055-9965-
dc.identifier.pmid18199707-
dc.identifier.doi10.1158/1055-9965.EPI-07-0751-
dc.identifier.urihttp://hdl.handle.net/10146/31874-
dc.description.abstractBACKGROUND: 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 action of Nudix hydrolase(s) on oxidative modification of the nucleotide pool is a likely candidate for the 8-oxodG found in urine and, potentially, of other oxidized 2'-deoxyribonucleoside lesions. Literature reports suggest that diet and cell death have minimal, if any, influence upon urinary levels of 8-oxodG and 8-oxo-7,8-dihydroguanine, although this should be assessed on a lesion-by-lesion basis. Broadly speaking, there is consensus between chromatographic techniques; however, ELISA approaches continue to overestimate 8-oxodG levels and is not sufficiently specific for accurate quantification. With increasing numbers of lesions being studied, it is vital that these fundamental issues are addressed. We report the formation of the European Standards Committee on Urinary (DNA) Lesion Analysis whose primary goal is to achieve consensus between methods and establish reference ranges in health and disease.en
dc.language.isoenen
dc.relation.urlhttp://cebp.aacrjournals.org/cgi/content/full/17/1/3en
dc.subjectCell Deathen
dc.subjectDNA damageen
dc.subjectDNA Repairen
dc.subjectDeoxyguanosineen
dc.subjectDieten
dc.subjectEnzyme-Linked Immunosorbent Assayen
dc.subjectOxidative Stressen
dc.subject.meshCell Death-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Repair-
dc.subject.meshDeoxyguanosine-
dc.subject.meshDiet-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshHumans-
dc.subject.meshOxidative Stress-
dc.titleMeasurement and meaning of oxidatively modified DNA lesions in urine.en
dc.typeArticleen
dc.identifier.journalCancer Epidemiology, Biomarkers & Prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncologyen

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