Central Laboratory and Radiation Biology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan .
J Radiat Res. 2010;51(3):251-5. doi: 10.1269/jrr.09069. Epub 2010 Mar 3.
Ataxia telangiectasia (AT) cells, with their defective double-strand break (DSB) repair processes, exhibit high sensitivity to low-LET radiation such as X-rays irradiation and gamma beams. Since heavy ion beam treatment for cancer is becoming increasingly common in Japan and elsewhere, it is important to also determine their sensitivity to high-LET radiation. For this purpose we irradiated AT and normal human cells immortalized with the human telomerase gene using high- (24-60 keV/microm carbon and 200 keV/microm iron ions) or low-LET (X-rays) radiation in non-proliferative conditions. In normal cells the RBE (relative biological effectiveness) of carbon and iron ions increased from 1.19 to 1.81 in proportion to LET. In contrast, their RBE in AT cells increased from 1.32 at 24 keV/microm to 1.59 at 40 keV/microm, and exhibited a plateau at over 40 keV/microm. In normal cells most gamma-H2AX foci induced by both carbon- and iron-ion beams had disappeared at 40 h. In AT cells, however, a significant number of gamma-H2AX foci were still observed at 40 h. The RBEs found in the AT cells after heavy-ion irradiation were consistent with the effects predicted from the presence of non-homologous end joining defects. The DSBs remaining after heavy-ion irradiation suggested defects in the AT cells' DSB repair ability.
毛细血管扩张共济失调症 (AT) 细胞的双链断裂 (DSB) 修复过程存在缺陷，对 X 射线和伽马射线等低 LET 辐射非常敏感。由于重离子束治疗癌症在日本和其他地方越来越普遍，因此确定它们对高 LET 辐射的敏感性也很重要。为此，我们使用高 LET（24-60 keV/μm 碳和 200 keV/μm 铁离子）或低 LET（X 射线）辐射在非增殖条件下辐照永生的 AT 和正常人类细胞。在正常细胞中，碳离子和铁离子的 RBE（相对生物效应）与 LET 成比例地从 1.19 增加到 1.81。相比之下，它们在 AT 细胞中的 RBE 从 24 keV/μm 时的 1.32 增加到 40 keV/μm 时的 1.59，并在超过 40 keV/μm 时呈现出平台。在正常细胞中，由碳离子和铁离子束诱导的大多数 γ-H2AX 焦点在 40 小时后消失。然而，在 AT 细胞中，在 40 小时后仍观察到大量的 γ-H2AX 焦点。重离子照射后在 AT 细胞中发现的 RBE 与非同源末端连接缺陷存在所预测的效果一致。重离子照射后残留的 DSB 表明 AT 细胞的 DSB 修复能力存在缺陷。
