Document Detail

Radiosensitization of mouse sarcoma cells by fludarabine (F-ara-A) or gemcitabine (dFdC), two nucleoside analogues, is not mediated by an increased induction or a repair inhibition of DNA double-strand breaks as measured by pulsed-field gel electrophoresis.
MedLine Citation:
PMID:  9652808     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To investigate the effect of fludarabine (F-ara-A) and gemcitabine (dFdC), two radiosensitizing nucleoside analogues, on the induction and repair of DNA dsb after ionizing radiation.
MATERIALS AND METHODS: Radiosensitization of mouse sarcoma SA-NH and FSA cells was studied using a clonogenic assay. Cell survival curves were fitted with the linear-quadratic model. DNA dsbs were detected by pulsed-field gel electrophoresis under neutral conditions.
RESULTS: F-ara-A (100 micromol dm(-3) for 1 h prior to irradiation) induced a substantial radiosensitization in SA-NH cells with a dose modification factor of 2.0 for a surviving fraction of 0.5. In a FSA mouse sarcoma cell line, dFdC (5 micromol dm(-3) for 3 h prior to irradiation) induced a modest radiosensitization with a DMF of 1.2 for a surviving fraction of 0.5. Under similar experimental conditions, neither F-ara-A nor dFdC altered the yield of radiation-induced DNA dsbs in the dose range of 0-40 Gy. After a single dose of 25 Gy (SA-NH cells) or 40 Gy (FSA cells), neither the kinetics of repair nor the amount of residual damage was affected by F-ara-A or dFdC.
CONCLUSIONS: For experimental conditions under which radiosensitization was observed, neither the induction nor the repair of DNA dsbs after ionizing radiation were affected by F-ara-A or dFdC.
V Grégoire; M Beauduin; M Bruniaux; B De Coster; M Octave Prignot; P Scalliet
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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:  73     ISSN:  0955-3002     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-07-16     Completed Date:  1998-07-16     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  511-20     Citation Subset:  IM; S    
UCL St-Luc University Hospital, Department of Radiation Oncology and Laboratory of Radiobiology, Brussels, Belgium.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Combined Modality Therapy
DNA Damage*
DNA Repair / drug effects*
DNA, Neoplasm / drug effects*,  metabolism,  radiation effects*
Deoxycytidine / analogs & derivatives*,  pharmacology
Electrophoresis, Gel, Pulsed-Field
Fibrosarcoma / drug therapy,  metabolism,  radiotherapy*
Mice, Inbred C3H
Radiation Tolerance / drug effects*
Radiation-Sensitizing Agents / pharmacology*
Tumor Cells, Cultured
Vidarabine / analogs & derivatives*,  pharmacology
Reg. No./Substance:
0/Antineoplastic Agents; 0/DNA, Neoplasm; 0/Radiation-Sensitizing Agents; 5536-17-4/Vidarabine; 951-77-9/Deoxycytidine; B76N6SBZ8R/gemcitabine; P2K93U8740/fludarabine

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