RADIOSENSITIZATION OF MOUSE SARCOMA-CELLS BY FLUDARABINE (F-ARA-A) ORGEMCITABINE (DFDC), 2 NUCLEOSIDE ANALOGS, IS NOT MEDIATED BY AN INCREASED INDUCTION OR A REPAIR INHIBITION OF DNA DOUBLE-STRAND BREAKS AS MEASURED BY PULSED-FIELD GEL-ELECTROPHORESIS

Purpose: To investigate the effect of fludarabine (F-ara-A) and gemcit abine (dFdC), two radiosensitizing nucleoside analogues, on the induct ion and repair of DNA dsb after ionizing radiation. Materials and meth ods: Radiosensitization of mouse sarcoma SA-NH and FSA cells was studi ed using a clonogenic assay. Cell survival curves were fitted with the linear-quadratic model. DNA dsbs were detected by pulsed-field gel el ectrophoresis under neutral conditions. Results: F-ara-A (100 mu mol d m(-3) for 1 h prior to irradiation) induced a substantial radiosensiti zation in SA-NH cells with a dose modification factor of 2.0 for a sur viving fraction of 0.5. In a FSA mouse sarcoma cell line, dFdC (5 mu m ol dm(-3) for 3 h prior to irradiation) induced a modest radiosensitiz ation 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 o f radiation-induced DNA dsbs in the dose range of 0-40 Gy. After a sin gle dose of 25 Gy (SA-NH cells) or 40 Gy (FSA cells), neither the kine tics of repair nor the amount of residual damage was affected by F-ara -A or dFdC. Conclusions: For experimental conditions under which radio sensitization was observed, neither the induction nor the repair of DN A dsbs after ionizing radiation were affected by F-ara-A or dFdC.