Institut de Radioprotection et de Sûreté Nucléaire (IRSN), BP 17, 92262 Fontenay-aux-Roses, France.
CHU Poitiers, Unité de Physique Médicale, Département de Radiothérapie, 86021 Poitiers, France.
Int J Mol Sci. 2022 Mar 29;23(7):3770. doi: 10.3390/ijms23073770.
Double-strand breaks (DSBs) in nuclear DNA represents radiation-induced damage that has been identified as particularly deleterious. Calculating this damage using Monte Carlo track structure modeling could be a suitable indicator to better assess and anticipate the side-effects of radiation therapy. However, as already demonstrated in previous work, the geometrical description of the nucleus and the DNA content used in the simulation significantly influence damage calculations. Therefore, in order to obtain accurate results, this geometry must be as realistic as possible. In this study, a new geometrical model of an endothelial cell nucleus and DNA distribution according to the isochore theory are presented and used in a Monte Carlo simulation chain based on the Geant4-DNA toolkit. In this theory, heterochromatin and euchromatin compaction are distributed along the genome according to five different families (L1, L2, H1, H2, and H3). Each of these families is associated with a different hetero/euchromatin rate related to its compaction level. In order to compare the results with those obtained using a previous nuclear geometry, simulations were performed for protons with linear energy transfers (LETs) of 4.29 keV/µm, 19.51 keV/µm, and 43.25 keV/µm. The organization of the chromatin fibers at different compaction levels linked to isochore families increased the DSB yield by 6-10%, and it allowed the most affected part of the genome to be identified. These new results indicate that the genome core is more radiosensitive than the genome desert, with a 3-8% increase in damage depending on the LET. This work highlights the importance of using realistic distributions of chromatin compaction levels to calculate radio-induced damage using Monte Carlo simulation methods.
双链断裂 (DSB) 是核 DNA 中辐射诱导的损伤，已被确定为特别有害的损伤。使用蒙特卡罗径迹结构建模来计算这种损伤可以作为更好地评估和预测放射治疗副作用的合适指标。然而，正如之前的工作已经证明的那样，模拟中核和 DNA 含量的几何描述会显著影响损伤计算。因此，为了获得准确的结果，这种几何形状必须尽可能地真实。在这项研究中，根据同缘理论提出了一种新的内皮细胞核和 DNA 分布的几何模型，并将其用于基于 Geant4-DNA 工具包的蒙特卡罗模拟链中。在该理论中，异染色质和常染色质根据五个不同的家族（L1、L2、H1、H2 和 H3）沿着基因组进行压缩。这些家族中的每一个都与不同的异染色质/常染色质率相关，该比率与其压缩水平有关。为了将结果与使用先前核几何形状获得的结果进行比较，针对线性能量转移 (LET) 为 4.29 keV/μm、19.51 keV/μm 和 43.25 keV/μm 的质子进行了模拟。与同缘家族相关的不同压缩水平的染色质纤维的组织增加了 6-10%的双链断裂产额，并能够识别基因组中受影响最严重的部分。这些新的结果表明，与基因组荒漠相比，基因组核心的放射敏感性更高，取决于 LET，损伤增加了 3-8%。这项工作强调了使用真实的染色质压缩水平分布来计算使用蒙特卡罗模拟方法的放射性损伤的重要性。
