Abstract
Radiation-induced bystander responses are biological effects observed in cells that receive signals from irradiated cells but are not directly exposed to ionizing radiations. Using a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, KEK, we recently showed that nitric oxide (NO)-mediated bystander cell killing is parabolically enhanced in a dose-dependent manner. In this study, we irradiated 5 nuclei of V79 cells with 10 × 10 µm2 5.35 keV X-ray beams and then measured the mutation frequency in the bystander cells by using the HPRT mutation assay. The mutation frequency with the null dose was 2.6 × 10-5 (background level) and decreased to 5.3 × 10-6 with a dose of approximately 1 Gy (absorbed-dose in the nucleus); at higher doses, however, the frequency returned to the background level. Same type of biphasic dose-response was observed during the bystander cell killing, as shown in our previous study. Similarity of these behaviors in dose-response may suggest a correlation between the enhancement of bystander cell killing and the suppression of spontaneous mutagenesis in the bystander cells. Increase in oxidative damage in unstable cells which have lost an antioxidative ability is responsible for spontaneous mutagenesis. The genetically unstable cells in the population of bystander cells might be selectively excluded by the bystander cell killing as NO caused mitochondrial degeneration, and hence the suppression of mutagenesis was observed in the bystander cells.
