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.
OBJECTIVE
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.


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.
Grégoire
V
V
UCL St-Luc University Hospital, Department of Radiation Oncology and Laboratory of Radiobiology, Brussels, Belgium.
Beauduin
M
M
Bruniaux
M
M
De Coster
B
B
Octave Prignot
M
M
Scalliet
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016521:Electrophoresis, Gel, Pulsed-Field; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D014740:Vidarabine; C024352:fludarabine; D000093542:Gemcitabine