Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, United States of America.
Department of Radiation Oncology, University of California San Francisco, United States of America.
Phys Med Biol. 2021 Jul 30;66(15). doi: 10.1088/1361-6560/ac15a5.
In radiopharmaceutical treatments-particles are employed to treat tumor cells. However, the mechanism that drives the biological effect induced is not well known. Being ionizing radiation,-particles can affect biological organisms by producing damage to the DNA, either directly or indirectly. Following the principle that microdosimetry theory accounts for the stochastic way in which radiation deposits energy in sub-cellular sized volumes via physical collisions, we postulate that microdosimetry represents a reasonable framework to characterize the statistical nature of direct damage induction by-particles to DNA. We used the TOPAS-nBio Monte Carlo package to simulate direct damage produced by monoenergetic alpha particles to different DNA structures. In separate simulations, we obtained the frequency-mean lineal energy (yF) and dose-mean lineal energy (yD) of microdosimetric distributions sampled with spherical sites of different sizes. The total number of DNA strand breaks, double strand breaks (DSBs) and complex strand breaks per track were quantified and presented as a function of eitheryForyD.The probability of interaction between a track and the DNA depends on how the base pairs are compacted. To characterize this variability on compactness, spherical sites of different size were used to match these probabilities of interaction, correlating the size-dependent specific energy (z) with the damage induced. The total number of DNA strand breaks per track was found to linearly correlate withyFandzFwhen using what we defined an effective volume as microdosimetric site, while the yield of DSB per unit dose linearly correlated withyDorzD,being larger for compacted than for unfolded DNA structures. The yield of complex breaks per unit dose exhibited a quadratic behavior with respect toyDand a greater difference among DNA compactness levels. Microdosimetric quantities correlate with the direct damage imparted on DNA.
在放射性药物治疗中，粒子被用于治疗肿瘤细胞。然而，驱动诱导生物学效应的机制尚不清楚。由于粒子是电离辐射，它可以通过直接或间接损伤 DNA 来影响生物机体。根据微剂量学理论，该理论解释了辐射通过物理碰撞在亚细胞大小的体积中随机沉积能量的原理，我们假设微剂量学代表了一种合理的框架，可以描述粒子对 DNA 直接损伤诱导的统计性质。我们使用 TOPAS-nBio 蒙特卡罗程序包模拟了单能阿尔法粒子对不同 DNA 结构造成的直接损伤。在单独的模拟中，我们获得了用不同大小的球形位点抽样的微剂量分布的频率平均线性能量（yF）和剂量平均线性能量（yD）。每个轨迹的 DNA 链断裂总数、双链断裂（DSB）和复杂链断裂的数量都被量化，并作为 yF 或 yD 的函数呈现。轨迹与 DNA 之间的相互作用的概率取决于碱基对的压缩程度。为了描述这种紧凑度的可变性，使用了不同大小的球形位点来匹配这些相互作用的概率，将与大小相关的特定能量（z）与诱导的损伤相关联。当我们将有效体积定义为微剂量学位点时，每个轨迹的 DNA 链断裂总数与 yF 和 zF 呈线性相关，而单位剂量的 DSB 产额与 yD 或 zD 呈线性相关，对于紧凑的 DNA 结构，其产额大于展开的 DNA 结构。单位剂量的复杂断裂产额与 yD 呈二次关系，与 DNA 紧凑度水平的差异更大。微剂量学量与 DNA 上的直接损伤相关。
