Direct action is the key to understand the high biological effects caused by particle beams

Hirayama, Ryoichi*; Matsumoto, Yoshitaka*; Uzawa, Akiko*; Takase, Nobuhiro*; Tsuruoka, Chizuru*; Wada, Mami*; Noguchi, Miho; Kase, Yuki*; Matsufuji, Naruhiro*; Ito, Atsushi*; Okayasu, Ryuichi*; Furusawa, Yoshiya*

The contribution of indirect action mediated by OH radicals in cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide (DMSO), which suppresses indirect action of radiation without affecting direct action. Exponentially growing Chinese hamster ovary cells under oxic and hypoxic conditions were exposed to X-rays and iron ions having a dose-averaged LET at 200 keV/micrometer in the presence or absence of DMSO, and the cell survival was determined using the colony formation assay. The contributions of indirect action of 76% and 50% were found for X-rays under oxic and hypoxic conditions, respectively. In contrast, the contributions of indirect action for iron ions were estimated to be 42% and 32%. The RBE values were 2.8 for oxic and 5.3 for hypoxic, and the OER values were 2.8 for X-rays and 1.5 for iron ions. When the RBE and OER were estimated separately for direct action (RBE(D) and OER(D)) and indirect action (RBE(I) and OER(I)); the RBE(D) was larger than RBE(I) under both normal and low oxygen concentrations. The OER(D) values for both X-rays and iron ions were lower than that for OER(I). Thus, direct action of radiation gives a remarkably higher RBE and lower OER for cell killing than indirect action. It is possible that particle beams may be highly effective in treating cancer if the particle therapy can only use the portion of direct action out of total radiation actions; this would be exemplified by the usage of radioactive 9C-ion beams and boron neutron capture.