Document Detail


Oxidative DNA damage and senescence of human diploid fibroblast cells.
MedLine Citation:
PMID:  7753808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Q Chen; A Fischer; J D Reagan; L J Yan; B N Ames
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
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:
Created Date:  1995-06-16     Completed Date:  1995-06-16     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4337-41     Citation Subset:  IM    
Affiliation:
Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Aging / 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:
CA39910/CA/NCI NIH HHS; ESO1896/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
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
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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