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    
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.
N Foray; A Priestley; G Alsbeih; C Badie; E P Capulas; C F Arlett; E P Malaise
Related Documents :
16540517 - Radiation-induced delayed cell death in a hypomorphic artemis cell line.
3011247 - Expression of potentially lethal damage in chinese hamster cells exposed to hematoporph...
8137287 - Interaction of ionizing radiation with the topoisomerase i poison camptothecin in growi...
12701807 - L-canavanine as a radiosensitization agent for human pancreatic cancer cells.
24196447 - Macromitophagy, neutral lipids synthesis, and peroxisomal fatty acid oxidation protect ...
11115547 - Bystander effect in uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide ge...
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    
Laboratoire de Radiobiologie, Institut Gustave-Roussy, Villejuif, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Ataxia Telangiectasia / pathology*
Cell Line
DNA / metabolism,  radiation effects*
DNA Damage*
Dose-Response Relationship, Radiation
Fibroblasts / metabolism,  physiology,  radiation effects*
Radiation Tolerance*
Reg. No./Substance:

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

Previous Document:  Elevated frequency of p53-independent apoptosis after irradiation increases levels of DNA breaks in ...
Next Document:  Enhancement of frequencies of restriction endonuclease-induced chromatid breaks by arabinoside adeni...