Aging and defense against generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in DNA.

2.50
Hdl Handle:
http://hdl.handle.net/10146/113464
Title:
Aging and defense against generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in DNA.
Authors:
Mikkelsen, Lone; Bialkowski, Karol; Risom, Lotte; Lohr, Mille; Loft, Steffen; Moller, Peter
Abstract:
The imbalance between the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in DNA and the efficiency of cellular systems of DNA protection and repair is considered an important factor in the age-dependent development of cancer. This study investigated the relationship between oxidatively damaged DNA and the activity of the DNA repair system and 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxodGTPase) activity in liver and lung tissue from mice at 10-100 weeks of age. The level of 8-oxodG increased with age, whereas the level of formamidopyrimidine DNA glycosylase sites was unaltered. The enzyme activity toward single oxygen-induced DNA damage and mRNA expression levels of Ercc1, Neil1, and Ogg1 remained unaltered with age. However, the 8-oxodGTPase activity in the liver was 18% (95% CI: 0.2-37%) lower in mice at 25 and 50 weeks than in 10-week-old mice. The 10- and 100-week-old mice had similar 8-oxodGTPase activity. In contrast, the mRNA expression of Nudt1 was statistically unaltered that likely resulted from higher variation of measurements. The accumulation of 8-oxodG with age is not a direct consequence of decreased enzyme activity toward singlet oxygen-induced substrate DNA. An age-related higher level of 8-oxodG even occurs concomitantly with high 8-oxodGTPase activity.
Citation:
Free Radic. Biol. Med. 2009, 47 (5):608-615
Journal:
Free Radical Biology & Medicine
Issue Date:
1-Sep-2009
URI:
http://hdl.handle.net/10146/113464
DOI:
10.1016/j.freeradbiomed.2009.05.030
PubMed ID:
19500668
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4WK4769-2&_user=1843694&_coverDate=09%2F01%2F2009&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=3151b156f224c1f7ee215fd5c0070692&searchtype=a
Type:
Article
Language:
en
ISSN:
1873-4596
Sponsors:
This study was supported by Danish Research Councils, 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), including a travel grant to Lone Mikkelsen, and by a scholarship from The Danish Cancer Society.
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Full metadata record

DC FieldValue Language
dc.contributor.authorMikkelsen, Loneen
dc.contributor.authorBialkowski, Karolen
dc.contributor.authorRisom, Lotteen
dc.contributor.authorLohr, Milleen
dc.contributor.authorLoft, Steffenen
dc.contributor.authorMoller, Peteren
dc.date.accessioned2010-10-19T11:38:56Z-
dc.date.available2010-10-19T11:38:56Z-
dc.date.issued2009-09-01-
dc.identifier.citationFree Radic. Biol. Med. 2009, 47 (5):608-615en
dc.identifier.issn1873-4596-
dc.identifier.pmid19500668-
dc.identifier.doi10.1016/j.freeradbiomed.2009.05.030-
dc.identifier.urihttp://hdl.handle.net/10146/113464-
dc.description.abstractThe imbalance between the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in DNA and the efficiency of cellular systems of DNA protection and repair is considered an important factor in the age-dependent development of cancer. This study investigated the relationship between oxidatively damaged DNA and the activity of the DNA repair system and 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxodGTPase) activity in liver and lung tissue from mice at 10-100 weeks of age. The level of 8-oxodG increased with age, whereas the level of formamidopyrimidine DNA glycosylase sites was unaltered. The enzyme activity toward single oxygen-induced DNA damage and mRNA expression levels of Ercc1, Neil1, and Ogg1 remained unaltered with age. However, the 8-oxodGTPase activity in the liver was 18% (95% CI: 0.2-37%) lower in mice at 25 and 50 weeks than in 10-week-old mice. The 10- and 100-week-old mice had similar 8-oxodGTPase activity. In contrast, the mRNA expression of Nudt1 was statistically unaltered that likely resulted from higher variation of measurements. The accumulation of 8-oxodG with age is not a direct consequence of decreased enzyme activity toward singlet oxygen-induced substrate DNA. An age-related higher level of 8-oxodG even occurs concomitantly with high 8-oxodGTPase activity.en
dc.description.sponsorshipThis study was supported by Danish Research Councils, 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), including a travel grant to Lone Mikkelsen, and by a scholarship from The Danish Cancer Society.en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4WK4769-2&_user=1843694&_coverDate=09%2F01%2F2009&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=3151b156f224c1f7ee215fd5c0070692&searchtype=aen
dc.subjectCell Agingen
dc.subjectDNA Damageen
dc.subjectDNA Repairen
dc.subjectDNA-Binding Proteinsen
dc.subjectDeoxyguanosineen
dc.subjectEndonucleasesen
dc.subjectGene Expression Regulationen
dc.subjectLiveren
dc.subjectAnimalsen
dc.subjectMiceen
dc.subject.meshAnimals-
dc.subject.meshCell Aging-
dc.subject.meshDNA-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Glycosylases-
dc.subject.meshDNA Repair-
dc.subject.meshDNA Repair Enzymes-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshDeoxyguanosine-
dc.subject.meshEndonucleases-
dc.subject.meshFemale-
dc.subject.meshGene Expression Regulation, Enzymologic-
dc.subject.meshLiver-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshPhosphoric Monoester Hydrolases-
dc.titleAging and defense against generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in DNA.en
dc.typeArticleen
dc.identifier.journalFree Radical Biology & Medicineen

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