量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Since 1994, a Phase I/II clinical study and radiotherapy have been carrying out using carbon-ion beams generated with the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences. Now we constructed the new treatment facility for the advanced carbon-ion therapy applying a 3D fast spot scanning system with pencil beams. To identify the biological effects of a spot scanning carbon-ion beams in vitro, we demonstrated cell-killing effect of human tumor cell lines using the spot scanning irradiation of carbon-ion microbeams generated with the Takasaki Ion Accelerators for Advanced Radiation Application (TIARA) in Japan Atomic Energy Agency. We irradiated either 4-cell lines with wild-type P53 or 4-cell lines with mutated-type P53 using the TIARA microbeams collimated by 20µm in diameter. We can easily estimate the number of the directly irradiated cells to be 0.01% level of the total cells on the dish using the highly controlled microbeam irradiation system. The percent survival in the cells with wild-type P53 was around 90%, while almost 100% was observed in the cells with mutated-type P53. We can expect the percent survival of 99.99% level when the cell-killing effect was induced in directly irradiated 0.01% cells, assuming no bystander effect. However, the percent in the cells with wild-type P53 was significantly low beyond our expectation. Moreover, the percent returned to 100% when using a specific inhibitor of gap-junction mediated cell-cell communication. The results are consistent with the data using the carbon-ion broad beams with the shielding method at HIMAC, which irradiation was carried out using 4 different protocols; (1) All cells were irradiated; (2) Irradiated and unirradiated cells were pooled in a 1:1 ratio as a single culture; (3) Half of cells were irradiated using beam stopper; and (4) Half of cells were irradiated with a specific inhibitor of gap-junction. Our overall results showed that bystander cell-killing effect was observed in the cells with wild-type P53, but not in the P53-mutated cells. There is clear evidence that the spot scanning irradiation system of carbon ions enables the enhanced cell killing in cells with wild-type P53 gene via gap-junction mediated bystander effect.
P53-dependent cell-killing effect via bystander effect using carbon-ion microbeams simulating the spot scanning system with pencil beams
