Comparison of cellular damage response to low-dose-rate 125I seed irradiation and high-dose-rate gamma irradiation in human lung cancer cells

To investigate the difference of cellular response between low-dose-rate (LDR) 125I seed irradiation and high-dose-rate (HDR) γ-irradiation in human lung cancer cells. A549 and NCI-H446 cells with or without wortmannin (WM) treatment were exposed to 125I seeds and γ-rays, respectively. Cell survival, micronuclei (MN) formation, and the expressions of Ku70/Ku80 proteins were measured. There was a strong negative correlation between survival and MN formation for both irradiations, and the MN inductions of NCI-H446 were about twofolds of those of A549, and the survival of NCI-H446 was lower than that of A549, indicating the radiosensitivity of NCI-H446 cells was greater than that of A549 cells. Interestingly, at 4-Gy radiation, NCI-H446 cells were more sensitive to LDR irradiation than HDR irradiation. WM treatment enhanced the radiosensitivity of A549 cells evenly to 125I seed and γ-irradiation, but this treatment led NCI-H446 cells to be more sensitive to LDR 125I. Further results revealed that the expression of phosphorylated Ku80 protein was enhanced in irradiated A549, but in contrast, it was markedly decreased in NCI-H446 cells after 4-Gy LDR 125I irradiation as that compared with γ-irradiated and nonirradiated cells. NCI-H446 cells were more sensitive to LDR 125I irradiation than HDR irradiation, and this sensitivity could be further enhanced by WM treatment. But no obvious differences of cellular response to both irradiations were observed in A549. Ku as molecular markers together with cell proliferation rate can be used to predict the radiosensitivity of tumor cells to LDR 125I seed irradiation.