a Radiobiology of Accidental Exposure Laboratory.
b Ionizing Radiation Dosimetry Laboratory.
Radiat Res. 2019 Jun;191(6):566-584. doi: 10.1667/RR15312.1. Epub 2019 Apr 25.
Advances in accelerator technology, which have enabled conforming radiotherapy with charged hadronic species, have brought benefits as well as potential new risks to patients. To better understand the effects of ionizing radiation on tumor and surrounding tissue, it is important to investigate and quantify the relationship between energy deposition at the nanometric scale and the initial biological events. Monte Carlo track structure simulation codes provide a powerful tool for investigating this relationship; however, their success and reliability are dependent on their improvement and development accordingly to the dedicated biological data to which they are challenged. For this aim, a microbeam facility that allows for fluence control, down to one ion per cell nucleus, was used to evaluate relative frequencies of DNA damage after interaction between the incoming ion and DNA according to radiation quality. Primary human cells were exposed to alpha particles of three different energies with respective linear energy transfers (LETs) of approximately 36, 85 or 170 keV·µm at the cells' center position, or to protons (19 keV·µm). Statistical evaluation of nuclear foci formation (53BP1/γ-H2AX), observed using immunofluorescence and related to a particle traversal, was undertaken in a large population of cell nuclei. The biological results were adjusted to consider the factors that drive the experimental uncertainties, then challenged with results using Geant4-DNA code modeling of the ionizing particle interactions on a virtual phantom of the cell nucleus with the same mean geometry and DNA density as the cells used in our experiments. Both results showed an increase of relative frequencies of foci (or simulated DNA damage) in cell nuclei as a function of increasing LET of the traversing particles, reaching a quasi-plateau when the LET exceeded 80-90 keV·µm. For the LET of an alpha particle ranging from 80-90 to 170 keV·µm, 10-30% of the particle hits did not lead to DNA damage inducing 53BP1 or γ-H2AX foci formation.
加速器技术的进步使得荷电重离子适形放疗成为可能，这给患者带来了益处，同时也带来了潜在的新风险。为了更好地了解电离辐射对肿瘤和周围组织的影响，研究和量化纳米尺度上能量沉积与初始生物事件之间的关系非常重要。蒙特卡罗径迹结构模拟代码为研究这种关系提供了一种强大的工具；然而，它们的成功和可靠性取决于它们根据所面临的特定生物数据进行相应的改进和发展。为此，使用微束设施来控制通量，使其达到每个细胞核一个离子，以评估根据辐射质量，入射离子与 DNA 相互作用后 DNA 损伤的相对频率。用人原代细胞分别用能量约为 36、85 或 170keV·µm 的三种不同能量的α粒子，或者质子（19keV·µm）在细胞中心位置进行照射。用免疫荧光法观察到核焦点形成（53BP1/γ-H2AX）的统计评估，并与粒子穿过相关，对大量细胞核进行了研究。用 Geant4-DNA 代码模拟细胞核虚拟模型中的离子粒子相互作用，将生物学结果调整到可以考虑到驱动实验不确定性的因素，并将结果与模型模拟结果进行了对比。细胞核的平均几何形状和 DNA 密度与我们实验中使用的细胞相同。结果都表明，随着穿过粒子的 LET 增加，焦点（或模拟 DNA 损伤）的相对频率在细胞核中增加，当 LET 超过 80-90keV·µm 时达到准平台。对于 LET 范围从 80-90keV·µm 到 170keV·µm 的α粒子，10-30%的粒子命中不会导致诱导 53BP1 或 γ-H2AX 焦点形成的 DNA 损伤。
