Document Detail

Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart.
MedLine Citation:
PMID:  17274981     Owner:  NLM     Status:  MEDLINE    
During the past several years increasing evidence indicating that the proliferation capacity of mammalian cells is highly radiosensitive, regardless of the species and the tissue of origin of the cells, has accumulated. It has also been shown that normal bone marrow cells of mice have a similar radiosensitivity to other mammalian cells so far tested. In this study, we investigated the genetic effects of ionizing radiation (2.5-15 Gy) on normal human mesenchymal stem cells and their telomerised counterpart hMSC-telo1. We evaluated overall genomic integrity, DNA damage/repair by applying a fluorescence-detected alkaline DNA unwinding assay together with Western blot analyses for phosphorylated H2AX and Q-FISH was applied for investigation of telomeric damage. Our results indicate that hMSC and TERT-immortalized hMSCs can cope with relatively high doses of gamma-rays and that overall DNA repair is similar in the two cell lines. The telomeres were extensively destroyed after irradiation in both cell types suggesting that telomere caps are especially sensitive to radiation. The TERT-immortalized hMSCs showed higher stability at telomeric regions than primary hMSCs indicating that cells with long telomeres and high telomerase activity have the advantage of re-establishing the telomeric caps.
Nedime Serakinci; Rikke Christensen; Jesper Graakjaer; Claire J Cairney; W Nicol Keith; Jan Alsner; Gabriele Saretzki; Steen Kolvraa
Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-08
Journal Detail:
Title:  Experimental cell research     Volume:  313     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-26     Completed Date:  2007-04-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1056-67     Citation Subset:  IM    
Department of Human Genetics, University of Aarhus, Aarhus, Denmark.
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MeSH Terms
Adult Stem Cells / enzymology,  metabolism*,  radiation effects
Aging / metabolism
Biological Markers / analysis
Cell Proliferation
Cell Survival
Cells, Cultured
Chromosomes / genetics,  metabolism,  radiation effects
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
DNA Damage
Histones / metabolism
In Situ Nick-End Labeling
Mesenchymal Stem Cells / enzymology,  metabolism*,  radiation effects
Models, Biological
Telomerase / genetics*,  metabolism,  physiology
Telomere / physiology,  radiation effects
Transduction, Genetic
Tumor Suppressor Protein p14ARF / metabolism
Tumor Suppressor Protein p53 / metabolism
beta-Galactosidase / physiology
Reg. No./Substance:
0/Biological Markers; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/H2AFX protein, human; 0/Histones; 0/Tumor Suppressor Protein p14ARF; 0/Tumor Suppressor Protein p53; EC protein, human; EC; EC

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