| Oxidative DNA damage and senescence of human diploid fibroblast cells. | |
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MedLine Citation:
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PMID: 7753808 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human diploid fibroblast cells cease growth in culture after a finite number of population doublings. To address the cause of growth cessation in senescent IMR-90 human fibroblast cells, we determined the level of oxidative DNA damage by using 8-oxoguanine excised from DNA and 8-oxo-2'-deoxyguanosine in DNA as markers. Senescent cells excise from DNA four times more 8-oxoguanine per day than do early-passage young cells. The steady-state level of 8-oxo-2'-deoxyguanosine in DNA is approximately 35% higher in senescent cells than in young cells. Measurement of protein carbonyls shows that senescent cells did not appear to have elevated protein oxidation. To reduce the level of oxidative damage, we cultured cells under a more physiological O2 concentration (3%) and compared the replicative life span to the cells cultured at the O2 concentration of air (20%). We found that cells grown under 3% O2 achieved 50% more population doublings during their lifetime. Such an extension of life span resulted from the delayed onset of senescence and elevation of growth rate and saturation density of cells at all passages. The spin-trapping agent alpha-phenyl-t-butyl nitrone (PBN), which can act as an antioxidant, also effectively delayed senescence and rejuvenated near senescent cells. The effect is dose-dependent and is most pronounced for cells at the stage just before entry into senescence. Our data support the hypothesis that oxidative DNA damage contributes to replicative cessation in human diploid fibroblast cells. |
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Authors:
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Q Chen; A Fischer; J D Reagan; L J Yan; B N Ames |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 92 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 1995 May |
Date Detail:
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Created Date: 1995-06-16 Completed Date: 1995-06-16 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4337-41 Citation Subset: IM |
Affiliation:
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Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Aging
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drug effects Cell Division / drug effects Cell Line Cyclic N-Oxides DNA Damage* Deoxyguanosine / analogs & derivatives, analysis Diploidy Dose-Response Relationship, Drug Fibroblasts / cytology, drug effects, physiology Guanine / analogs & derivatives, analysis Humans Kinetics Nitrogen Oxides / pharmacology* Oxygen / toxicity* Spin Labels Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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CA39910/CA/NCI NIH HHS; ESO1896/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclic N-Oxides; 0/Nitrogen Oxides; 0/Spin Labels; 3376-24-7/phenyl-N-tert-butylnitrone; 5614-64-2/8-hydroxyguanine; 73-40-5/Guanine; 7782-44-7/Oxygen; 88847-89-6/8-oxo-7-hydrodeoxyguanosine; 961-07-9/Deoxyguanosine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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