Physics Department, Clatterbridge Cancer Centre, Bebington, UK.
Br J Radiol. 2012 Dec;85(1020):e1242-8. doi: 10.1259/bjr/28365782.
This work explores the biological basis of a mechanistic model of radiation-induced lung damage; uniquely, the model makes a connection between the cellular radiobiology involved in lung irradiation and the full three-dimensional distribution of radiation dose.
Local tissue damage and loss of global organ function, in terms of radiation pneumonitis (RP), were modelled as different levels of radiation injury. Parameters relating to the former could be derived from the local dose-response function, and the latter from the volume effect of the organ. The literature was consulted to derive information on a threshold dose and volume-effect mechanisms.
Simulations of local tissue damage supported the alveolus as a functional subunit (FSU) which can be regenerated from a single surviving stem cell. A moderate interpatient variation in stem cell radiosensitivity (15%) resulted in a great variation in tissue response between 8 and 20 Gy. The threshold of FSU inactivation within a critical functioning volume leading to RP was found to be approximately 47% and the degree of health status variation (influencing the volume effect) in a population was estimated at 25%.
This work has shown that it is possible to make sense of the way the lung responds to radiation by modelling RP mechanistically, from cell death to tissue damage to loss of organ function.
Simulations were able to provide parameter values, currently not available in the literature, related to the response of the lung to irradiation.
本研究旨在探索放射性肺损伤机制模型的生物学基础；该模型独特之处在于，它将涉及肺照射的细胞放射生物学与辐射剂量的全三维分布联系起来。
局部组织损伤和整体器官功能丧失（即放射性肺炎）被建模为不同程度的辐射损伤。前者的参数可从局部剂量反应函数中得出，后者则来自器官的体积效应。查阅文献以获取有关剂量阈值和体积效应机制的信息。
局部组织损伤的模拟支持肺泡作为一个功能亚单位（FSU），它可以由单个存活的干细胞再生。干细胞放射敏感性的个体间中度差异（15%）导致 8 至 20 Gy 之间组织反应的巨大差异。导致放射性肺炎的 FSU 失活的临界功能体积中的阈值约为 47%，人群中健康状况变化的程度（影响体积效应）估计为 25%。
本研究表明，通过从细胞死亡到组织损伤再到器官功能丧失，对放射性肺炎进行机制建模，可以理解肺部对辐射的反应方式。
模拟能够提供目前文献中尚未提供的与肺对辐射反应相关的参数值。
