Document Detail

FANCD2-deficient human fibroblasts are hypersensitive to ionising radiation at oxygen concentrations of 0% and 3% but not under normoxic conditions.
MedLine Citation:
PMID:  19466639     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Individuals suffering from Fanconi Anemia (FA) exhibit a pronounced hypersensitivity to agents that cause DNA inter-strand crosslinks and frequently also to ionising radiation. However, fibroblast lines derived from FA patients generally show little or no radiosensitivity in vitro. Here, we sought to elucidate the role of the central FA protein D2 (FANCD2) in determining cellular radioresistance.
MATERIAL AND METHODS: Clonogenic radiation survival was assessed in an isogenic pair of human fibroblasts with or without wild-type FANCD2 under varying oxygen concentrations. Additional endpoints included single-cell gel electrophoresis, RAD51 foci formation, and apoptosis.
RESULTS: At 20% oxygen, there was no reduction in the survival of FANCD2-deficient fibroblasts compared to wild-type complemented cells. However, at 0% oxygen FANCD2-deficient cells were more radiosensitive than wild-type cells. Interestingly, at 3% oxygen, which more closely resembles the physiological environment in human tissues, the difference in radiosensitivity was maintained. Our data also suggest that the increased radiosensitivity of FANCD2-deficient cells seen under conditions of reduced oxygen is associated with apoptotic cell death, but not secondary to a defect in the homologous recombination repair pathway that is required for crosslink repair.
CONCLUSIONS: Our data may help explain the previously described discrepancy between the clinical and cellular radiosensitivity of FA patients.
Verena M Kuhnert; Lisa A Kachnic; Li Li; Martin Purschke; Liliana Gheorghiu; Richard Lee; Kathryn D Held; Henning Willers
Related Documents :
20084089 - A microwell array device capable of measuring single-cell oxygen consumption rates.
15696509 - Role of nutrient supply on cell growth in bioreactor design for tissue engineering of h...
7765589 - High density culture of mammalian cells with dynamic perfusion based on on-line oxygen ...
25170299 - Heterogeneity of osteosarcoma cell lines led to variable responses in reprogramming.
6718689 - The effect on the km for radiosensitization at 0 degree c of thiol depletion by diethyl...
20636139 - Antioxidants counteract nicotine and promote migration via racgtp in oral fibroblast ce...
11089929 - Contribution of single somites to the skeleton and muscles of the occipital and cervica...
10775159 - Development rates of male bovine nuclear transfer embryos derived from adult and fetal ...
11607199 - Efficient transformation and regeneration of rice small cell groups.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation biology     Volume:  85     ISSN:  0955-3002     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-25     Completed Date:  2009-08-12     Revised Date:  2013-09-04    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  523-31     Citation Subset:  IM; S    
Department of Radiation Oncology, University of Lübeck, Lübeck, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Anoxia / metabolism
Apoptosis / radiation effects
Cell Line
Fanconi Anemia Complementation Group D2 Protein / deficiency*,  metabolism
Fibroblasts / drug effects,  enzymology*,  metabolism,  radiation effects*
Oxygen / pharmacology*
Rad51 Recombinase / genetics
Radiation Tolerance* / genetics
Radiation, Ionizing
Recombination, Genetic / radiation effects
Reproducibility of Results
Grant Support
P01 CA095227/CA/NCI NIH HHS; P01 CA095227/CA/NCI NIH HHS
Reg. No./Substance:
0/Fanconi Anemia Complementation Group D2 Protein; 7782-44-7/Oxygen; EC 2.7.7.-/Rad51 Recombinase

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

Previous Document:  Selecting a measurement model for the analysis of the national institutes of health stroke scale.
Next Document:  Laser lipolysis of the arm, with and without suction aspiration: Clinical and histologic changes.