Document Detail


Hypersensitivity of ataxia telangiectasia fibroblasts to ionizing radiation is associated with a repair deficiency of DNA double-strand breaks.
MedLine Citation:
PMID:  9298107     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have studied the intrinsic radiosensitivity, repair of potentially lethal damage (PLD) and the repair rate of radiation-induced DNA double-strand breaks (DSB) in 11 non-transformed human fibroblast cell lines, four of which were homozygous for the A-T mutation and two that were heterozygous (A-TH). All the experiments were done on cells in plateau phase of growth (97-99% of cells in G0/G1). With a dose of 30 Gy delivered at 4 degrees C, the A-T cell lines had faster repair rates of up to 6 h, after which the repair curve crossed that of the control so that the residual damage at 24 h was higher in the A-T cells. Irradiation at 37 degrees C at low dose rate 1 cGy.min-1) produced even more marked differences between the A-T cells and controls: the residual DSB level was always higher in A-T cells than controls at doses of 5-40 Gy, due to defective repair of a small fraction of DSB in A-T cells. The two protocols showed DSB repair rates for the A-TH cell lines that were intermediate between those of the A-T and control cells. There was a quantitative relationship between the residual DSB after irradiation at 37 degrees C and the intrinsic radiosensitivity, and with the extent of PLD repair. There were very few apoptotic cells in the non-transformed control and A-T cell line, both before and after irradiation. In combination, these result support the contention that the defective repair of DSB is a mechanism of the hypersensitivity linked to the A-T mutation.
Authors:
N Foray; A Priestley; G Alsbeih; C Badie; E P Capulas; C F Arlett; E P Malaise
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation biology     Volume:  72     ISSN:  0955-3002     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-10-08     Completed Date:  1997-10-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  271-83     Citation Subset:  IM; S    
Affiliation:
Laboratoire de Radiobiologie, Institut Gustave-Roussy, Villejuif, France.
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MeSH Terms
Descriptor/Qualifier:
Ataxia Telangiectasia / pathology*
Cell Line
DNA / metabolism,  radiation effects*
DNA Damage*
Dose-Response Relationship, Radiation
Fibroblasts / metabolism,  physiology,  radiation effects*
Humans
Kinetics
Radiation Tolerance*
Temperature
Chemical
Reg. No./Substance:
9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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