Germanium oxide enhances the radiosensitivity of cells

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.