In vitro and in vivo Biological Responses of Proton Irradiation from MC-50 Cyclotron

In this study, we investigated the biological damage and stress responses induced by ion beam (proton beam) irradiation as a basis for the development of protective measures against space radiation. We examined the biological effects of proton beam produced by MC-50 cyclotron at KIRAMS on the cultured cells and mice. The proton beam energy used in this study was 34.9 MeV and the absorption dose rate for cells and mice were $0.509Gy\;sec^{-1}$ and $0.65Gy\;sec^{-1}$, respectively. The cell survival rates measured by plating efficiency showed the different sensitivity and dose-relationship between CHO cells and Balb/3T3 cells. HGPRT gene mutation frequency in Balb/3T3 was $15{\times}10^{-6}Gy^{-1}$, which was similar to the reported value of X-ray. When stress signaling proteins were examined in Balb/3T3 cells, $I{\kappa}B-{\alpha}$ decreased markedly whereas p53, phospho-p53, and Rb increased after proton beam irradiation, which implied that the stress signaling pathways were activated by proton beam irradiation. In addition, cellular senescence was induced in IMR-90 cells. In the experiments with C57BL/6 mouse, the immune cells (white blood cells, lymphocytes) in the peripheral blood were greatly reduced following proton beam irradiation whereas red blood cells and platelets showed relatively little change. These results can be utilized as basic data for studying the biological effects of proton beam using MC-50 cyclotron with respect to proton therapy research as well as space radiation research.