Bystander effects in tumor-free and tumor-bearing rat brains following irradiation by synchrotron X-rays

PURPOSE: Synchrotron microbeam radiation therapy (MRT) is a radiosurgery concept in the preclinical stage, developed mainly for brain tumor treatment. Experimental studies suggest that with MRT a better therapeutic index can be obtained than with homogenous field radiotherapy, but the underlying cellular mechanisms need further understanding. The aim of this study was to investigate the dynamics of radiation-induced bystander effects (RIBE) in rats after exposing one brain hemisphere to either MRT or homogenous synchrotron radiation (HSR). MATERIALS AND METHODS: Healthy and tumor-bearing Wistar rats were exposed to doses of 17.5, 35, 70 or 350 Gy, applied either as MRT or HSR to the right cerebral hemisphere. Rats were euthanized at 4, 8 and 12 hours after irradiation to assess the release of bystander signals. Brains and urinary bladders were dissected, and explants for bystander clonogenic reporter assays were set up. RESULTS: Clonogenic survival showed that RIBE occurred in both the non-irradiated brain hemisphere and in bladder of normal and tumor-bearing rats, while the irradiated hemisphere showed the direct effects of radiation. CONCLUSION: The RIBE observed in our reporter cells shows that both MRT and HSR yield a demonstrable abscopal effect after high doses of irradiation; presumably as part of a systemic response.