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

粒子線の生物効果における直接作用の重要性

平山 亮一*; 松本 孔貴*; 鵜沢 玲子*; 高瀬 信宏*; 鶴岡 千鶴*; 和田 麻美*; 野口 実穂; 加瀬 優紀*; 松藤 成弘*; 伊藤 敦*; 岡安 隆一*; 古澤 佳也*

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

OHラジカルが介在する間接作用の細胞死への寄与はDMSOを用いた最大防護寄与率から評価することができる。対数増殖期のCHO細胞を用い、これらを酸素存在下、及び低酸素化でX線、及びLET200keV/mの鉄イオン線を照射し、DMSO存在下、及び非存在下でコロニー形成法により細胞生存率を調べた。X線での間接作用の寄与は酸素下で76%、低酸素下で50%であった。これとは対照的に、鉄イオン線での間接作用寄与率は酸素下42%、低酸素下32%であった。RBE値は酸素下で2.8、低酸素下で5.3、OERはX線で2.8、鉄イオン線で1.5であった。直接作用のRBEは正常酸素下、及び低酸素下で間接作用のRBEより高い値となった。また、X線、及び鉄イオン線における直接作用のOERは間接作用のOERよりも低い値となった。もし、粒子線治療で直接作用のみを取り出して利用できるならば、粒子線は癌治療に非常に有効な治療法であると考えられる。これは炭素イオンビームや中性子捕捉療法の利用がよい実例である。

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.