Cell-cell communication mediated bystander effects from carbon-ion irradiated tumor to non-irradiated normal cells

Communication between tumor and normal cells is one of the important concerns for heavy-ion radiotherapy. We focused on the communication from carbon-ion irradiated tumor to non-irradiated bystander normal cells. Human glioblastoma cells (T98G) were irradiated with carbon-ion broadbeams (LET=73keV/µm) scheduled to either a single dose or three-fraction doses during three consecutive days at the Heavy Ion Medical Accelerator in Chiba (HIMAC) or carbon-ion microbeams (LET=103keV/µm) at the Takasaki Ion Accelerators for Advanced Radiation Application (TIARA). Then normal human fibroblasts were co-cultured with the T98G cells in presence or absence of a gap-junction inhibitor using the transwell permeable support system. After 24h bystander normal fibroblasts were assayed for cell killing and gene mutation at HPRT locus. The single-dose irradiation for both broadbeams and microbeams in absence of the gap-junction inhibitor resulted in increased cell-killing effect and mutation in the bystander normal cells. On the other hand, the fraction-dose irradiation of broadbeams showed higher in mutation than the single-dose irradiation, but the same level of cell-killing effect with the control. In the case of presence of the inhibitor, no differences were observed in both endpoints. There is clear evidence that the irradiated tumor cells enable to induce damage in the neighboring non-irradiated normal cells via the gap-junction mediated bystander effect.日本放射線影響学会第６０回大