Institute of Radiation Protection, Department of Radiation Sciences, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Department of Physics, East Carolina University, Greenville, NC, USA.
Sci Rep. 2017 Mar 27;7:45161. doi: 10.1038/srep45161.
Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25-256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs. The simulations show that protons and helium ions induce more DNA damage than heavier ions do at the same LET. With increasing LET, less DNA strand breaks are formed per unit dose, but due to their clustering the yields of double-strand breaks (DSB) increase, up to saturation around 300 keV/μm. Also individual DSB tend to cluster; DSB clusters peak around 500 keV/μm, while DSB multiplicities per cluster steadily increase with LET. Remarkably similar to patterns known from cell survival studies, LET-dependencies with pronounced maxima around 100-200 keV/μm occur on nanometre scale for sites that contain one or more DSB, and on micrometre scale for megabasepair-sized DNA fragments.
已针对能量为 0.25-256 MeV/u 的氢、氦、碳、氮、氧和氖离子,模拟了人细胞中的径迹结构和由此产生的 DNA 损伤。根据氢的离子相互作用截面,对所需的离子相互作用截面进行了缩放;对 Barkas 缩放公式进行了改进,将其适用范围扩展到约 10 keV/u,并利用已建立的阻止本领数据进行了验证。线性能量转移(LET)是根据细胞核中能量沉积来计算的;对于非常低能量的离子,它在薄片中局部定义。模拟表明,与相同 LET 的重离子相比,质子和氦离子会导致更多的 DNA 损伤。随着 LET 的增加,单位剂量形成的 DNA 链断裂减少,但由于其聚类,双链断裂(DSB)的产率增加,在 300 keV/μm 左右达到饱和。单个 DSB 也会聚类;DSB 簇在 500 keV/μm 左右达到峰值,而每个簇的 DSB 倍数则随着 LET 的增加而稳步增加。令人惊讶的是,与细胞存活研究中已知的模式相似,在包含一个或多个 DSB 的位点上,纳米尺度的 LET 依赖性在 100-200 keV/μm 左右出现明显的最大值,而在兆碱基对大小的 DNA 片段上,微米尺度的 LET 依赖性在 100-200 keV/μm 左右出现明显的最大值。