Abstract
We investigated here the combined effect of GeO 2 and radiation on cell viability. Cells were treated with 0 to 22 mM GeO 2 for 12 h followed by 1 Gy X irradiation. A synergistic cytotoxic effect was observed for the combined treatment with a dose-dependent reduction of cell viability. Complete survival curves showed a 2.3- and 2.75-fold increase in radiosensitivity for 50% cell death in the presence of 5 and 15 mM GeO 2 , respectively. The increased radiosensitivity also occurred when GeO 2 was given either 4 h prior to irradiation or immediately after radiation exposure. GeO 2 did not affect the total soluble thiol content or the activities of catalase and glutathione S-transferase. Analysis of the production of reactive oxygen species (ROS) revealed that the combined treatment dramatically increased the synthesis of ROS. Addition of N-acetyl cysteine (NAC, 20 mM) decreased the production of ROS in cells. NAC, however, increased cell viability only slightly after treatment with GeO 2 and radiation. Thus increased production of ROS makes little or no contribution to the observed death. The combination of GeO 2 and X radiation, however, significantly increased the frequency of DNA double-strand breaks (DSBs). Notably, the presence of GeO 2 also reduced the efficiency of DNA repair. We conclude that treatment with GeO 2 followed by X irradiation increases DNA DSBs and cell death. © 2003 by Radiation Research Society.