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.

Grégoire, Vincent;Beauduin, M.;Bruniaux, M;De Coster, B;Scalliet, Pierre;et.al.
(1998) International Journal of Radiation Biology — Vol. 73, n° 5, p. 511-520 (1998)

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  • Grégoire, VincentUCLouvain
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  • Beauduin, M.
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  • Bruniaux, M
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  • De Coster, B
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  • Scalliet, PierreUCLouvain
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Abstract
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.
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Grégoire, V., Beauduin, M., Bruniaux, M., De Coster, B., Octave Prignot, M., & Scalliet, P. (1998). 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. International Journal of Radiation Biology, 73(5), 511-520. https://hdl.handle.net/2078.5/133047 (Original work published 1998)