Document Detail


Accelerated telomere shortening and telomere abnormalities in radiosensitive cell lines.
MedLine Citation:
PMID:  15966765     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined telomere maintenance in cells of 11 primary fibroblast cell lines with differing genetic defects that confer sensitivity to ionizing radiation. These included cell lines derived from patients with ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi anemia, defective Artemis, DNA ligase I and DNA ligase IV, an immunodeficient patient with a defect in DNA double-strand break repair, and a patient diagnosed with xeroderma pigmentosum who, in addition, showed severe clinical sensitivity to ionizing radiation. Our results, based on Southern blot, flow-FISH and Q-FISH (quantitative FISH) measurements, revealed an accelerated rate of telomere shortening in most cell lines derived from the above patients compared to cell lines from normal individuals or a cell line isolated from a heterozygotic parent of one radiosensitive patient. This accelerated telomere shortening was accompanied by the formation of chromatin bridges in anaphase cells, indicative of the early loss of telomere capping function and in some cases low levels of chromosome abnormalities in metaphase cells. We also analyzed telomere maintenance in mouse embryonic stem cells deficient in Brca1, another defect that confers radiosensitivity. Similarly, these cells showed accelerated telomere shortening and mild telomere dysfunction in comparison to control cells. Our results suggest that mechanisms that confer sensitivity to ionizing radiation may be linked with mechanisms that cause telomere dysfunction.
Authors:
E Cabuy; C Newton; G Joksic; L Woodbine; B Koller; P A Jeggo; P Slijepcevic
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Radiation research     Volume:  164     ISSN:  0033-7587     ISO Abbreviation:  Radiat. Res.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-21     Completed Date:  2005-08-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0401245     Medline TA:  Radiat Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  53-62     Citation Subset:  IM; S    
Affiliation:
Brunel Institute of Cancer Genetics and Pharmacogenomics, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex, UB8 3PH, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Survival / genetics*,  radiation effects*
Chromosome Aberrations*
Dose-Response Relationship, Radiation
Fibroblasts / physiology,  ultrastructure
Humans
Mice
Radiation Dosage
Radiation Tolerance / genetics*
Stem Cells / physiology,  ultrastructure
Telomere / genetics*,  ultrastructure
Grant Support
ID/Acronym/Agency:
CA82423/CA/NCI NIH HHS

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