Energy deposition to the cytoplasm suppress bystander cell death which depend on the distance between irradiated cells and bystander cells

Bystander responses are phenomena in which cells adjacent to those that have been traversed by charged particles exhibit biological responses. Microbeam cell irradiation systems, which enable the observation of cellular responses of both non-irradiated and irradiated individual cells, are powerful tools for elucidating the mechanisms underlying these effects. We have been studying the differences in the lethal effects on V79 cells irradiated with microbeams of different sizes using synchrotron X-ray microbeam irradiation system developed at Photon Factory, KEK.<br>In a previous study, we observed a transient enhancement in bystander cell death in a dose-dependent manner when the nuclei alone were irradiated at low doses. On the other hand, the surviving fraction of bystander cells decreased monotonously when whole cells were irradiated. Moreover, addition of carboxy-PTIO, a specific scavenger of nitric oxide, NO, suppresses bystander cell death under both irradiation conditions. These results suggest that NO acts as a mediator in the induction of 2 types of bystander cell death, namely, the transient type and the monotonous type.<br>Recently, from the spatial analysis, we found that the transient type bystander cell death was principally induced in cells located within 1 mm from the irradiated cells, whereas majority of the monotonous type bystander cell death occurred in cells located beyond 1 mm from irradiated cells. Our findings clearly demonstrate that the induction of bystander cell death depend on the distance between irradiated cells and bystander cells and also on the energy-deposition sites in irradiated cells.