Cellular response to fludarabine treatment in combination with different ionizing radiation in renal carcinoma 786-O cells / 中华放射肿瘤学杂志

ABSTRACT

Objective To investigate DNA double-strand breaks and radiosensitization in renal carcinoma 786-O cells induced by fludarabine (FA) combined with different ionizing radiations.Methods The 786-O cells were exposed to FA combined with X-ray or heavy ion beam irradiation.Flow cytometry was used to evaluate the percentage of γH2AX-positive cells and cell cycle.The neutral comet assay was used to detect DNA double-strand breaks.The colony-forming assay was used to evaluate the effects of different treatments on cell survival.Comparison between groups was made by one-way analysis of variance or Dunnet' s t test.Results Compared with FA alone or irradiation alone,FA combined with different ionizing radiations increased DNA double-strand breaks as shown by significantly increased levels of γH2AX (P=0.007,0.001);FA combined with heavy ion beam irradiation lead to a cell cycle block at the radiosensitive G2/M phase and significantly increased the expression of γH2AX in the G2/M phase (P=0.000,0.000);the neutral comet assay revealed that FA combined with irradiation significantly increased DNA sublethal damage (P=0.020,0.060);FA significantly reduced the colony-forming rate after irradiation (P=0.000,0.030;0.001,0.040).Conclusions FA enhances the effects induced by X-ray and heavy ion beam irradiation with different properties.Particularly,FA substantially enhances the cell death induced by heavy ion beam irradiation.