Nuclear Science and Engineering Center, Japan Atomic Energy Agency, Tokai, Japan.
Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
Phys Med Biol. 2023 Apr 19;68(9). doi: 10.1088/1361-6560/acc720.
. The delivery of intensity-modulated radiation fields has improved the conformity of dose to tumour targets during radiotherapy (RT). Previously, it has been shown that intercellular communication between cells positioned in- and outside of the radiation field impacts cellular radiosensitivity under hypoxic and normoxic conditions. However, the mechanism of intercellular communication in hypoxia remains to be fully understood. In this study, the cell-killing effects of intercellular communication in hypoxia were modelled in an effort to better understand the underlying mechanisms of response.. By irradiating a 50% area of the culture dish (half-field exposure), experimental dose-response curves for cell survival and residual DNA double-strand breaks (DSBs) were generated in prostate (DU145) and non-small cell lung cancer (H1299) cells. The oxygen enhancement ratio (OER) was determined from early DSB yields (corresponding to relative direct damage) and used to model the in- and out-of-field radiosensitivity.. The developed integrated microdosimetric-kinetic (IMK) model successfully predicted the experimental dose responses for survival and lethal lesions, and provides a mechanistic interpretation that the probability of hits for releasing cell-killing signals is dependent on oxygen. This experimental and modelling study also suggests that residual DSBs correspond to logarithmic survival fraction (meaning lethal lesions) for in- and out-of-field cells. Our data suggest that the OER value determined using uniform-field exposure can be applied to predict the in- and out-of-field radiosensitivity of cells following exposure to intensity modulated beams.. The developed IMK model facilitates a more precise understanding of intercellular signalling following exposure to intensity-modulated radiation fields.
. 调强放射治疗（intensity-modulated radiation therapy，IMRT）提高了肿瘤靶区的剂量适形度。此前，有研究表明，辐射场内和场外的细胞之间的细胞间通讯会影响低氧和常氧条件下的细胞放射敏感性。然而，低氧条件下细胞间通讯的机制仍有待充分理解。在本研究中，通过模拟细胞间通讯在低氧条件下的细胞杀伤效应，旨在更好地理解反应的潜在机制。通过对培养皿的 50%区域进行照射（半野照射），在前列腺（DU145）和非小细胞肺癌（H1299）细胞中生成了细胞存活和残留 DNA 双链断裂（double-strand breaks，DSBs）的实验剂量-反应曲线。从早期 DSB 产量（对应于相对直接损伤）确定了氧增强比（oxygen enhancement ratio，OER），并用于模拟场内和场外的放射敏感性。所开发的综合微剂量-动力学（integrated microdosimetric-kinetic，IMK）模型成功预测了存活和致死损伤的实验剂量反应，并提供了一种机制解释，即释放杀伤信号的命中概率取决于氧。这项实验和建模研究还表明，残留的 DSB 对应于场内和场外细胞的对数存活分数（意味着致死损伤）。我们的数据表明，使用均匀场照射确定的 OER 值可用于预测细胞在接受调强束照射后的场内和场外放射敏感性。所开发的 IMK 模型有助于更精确地理解暴露于调强放射场后的细胞间信号。
