Bystander Effects Induced by Continuous Low-Dose-Rate 125I Seeds Potentiate the Killing Action of Irradiation on Human Lung Cancer Cells In Vitro

Abstract

To investigate bystander effects of low-dose-rate (LDR) (125)I seed irradiation on human lung cancer cells in vitro. A549 and NCI-H446 cell lines of differing radiosensitivity were directly exposed to LDR (125)I seeds irradiation for 2 or 4 Gy and then cocultured with nonirradiated cells for 24 hours. Induction of micronucleus (MN), gammaH2AX foci, and apoptosis were assayed. After 2 and 4 Gy irradiation, micronucleus formation rate (MFR) and apoptotic rate of A549 and NCI-H446 cells were increased, and the MFR and apoptotic rate of NCI-H446 cells was 2.1-2.8 times higher than that of A549 cells. After coculturing nonirradiated bystander cells with (125)I seed irradiated cells for 24 hours, MFR and the mean number of gammaH2AX foci/cells of bystander A549 and NCI-H446 cells were similar and significantly higher than those of control (p <0.05), although they did not increase with irradiation dose. However, the proportion of bystander NCI-H446 cells with MN numbers >/=3 and gammaH2AX foci numbers 15-19 and 20-24 was higher than that of bystander A549 cells. In addition, dimethyl sulfoxide (DMSO) treatment could completely suppress the bystander MN of NCI-H446 cells, but it suppressed only partly the bystander MN of A549 cells, indicating that reactive oxygen species are involved in the bystander response to NCI-H446 cells, but other signaling factors may contribute to the bystander response of A549 cells. Continuous LDR irradiation of (125)I seeds could induce bystander effects, which potentiate the killing action on tumor cells and compensate for the influence of nonuniform distribution of radiation dosage on therapeutic outcomes.