Abstract：
There has been some controversy over the use of radiobiological models when modeling the dose-response curves of ionizing radiation (IR)-induced chromosome aberration and tumor prevalence, as those curves usually show obvious non-targeted effects (NTEs) at low doses of high linear energy transfer (LET) radiation. The lack of understanding the contribution of NTEs to IR-induced carcinogenesis can lead to distinct deviations of relative biological effectiveness (RBE) estimations of carcinogenic potential, which are widely used in radiation risk assessment and radiation protection. In this work, based on the initial pattern of two classes of IR-induced DNA double-strand breaks (DSBs) clustering in chromatin domains and the subsequent incorrect repair processes, we proposed a novel radiobiological model to describe the dose-response curves of two carcinogenic-related endpoints within the same theoretical framework. The representative experimental data was used to verify the consistency and validity of the present model. The fitting results indicated that, compared with targeted effect (TE) and NTE models, the current model has better fitting ability when dealing with the experimental data of chromosome aberration and tumor prevalence induced by multiple types of IR with different LETs. Notably, the present model without introducing an NTE term was adequate to describe the dose-response curves of IR-induced chromosome aberration and tumor prevalence with NTEs in low-dose regions. Based on the fitting parameters, the LET-dependent RBE values were calculated for three given low doses. Our results showed that the RBE values predicted by the current model gradually decrease with the increase of doses for the endpoints of chromosome aberration and tumor prevalence. In addition, the calculated RBE was also compared with those evaluated from other models. These analyses show that the proposed model can be used as an alternative tool to well describe dose-response curves of multiple carcinogenic-related endpoints and effectively estimate RBE in low-dose regions.
摘要：
在对电离辐射（IR）诱导的染色体畸变和肿瘤患病率的剂量反应曲线进行建模时，使用放射生物学模型存在一些争议，因为这些曲线通常在低剂量的高线性能量转移(LET)辐射下显示明显的非靶向效应(NTE)。缺乏了解NTE对IR诱导的致癌作用的贡献可能导致对致癌潜力的相对生物有效性（RBE）估计的明显偏差，广泛应用于辐射风险评估和辐射防护。在这项工作中,基于染色质域中两类IR诱导的DNA双链断裂（DSB）聚类的初始模式以及随后的错误修复过程，我们提出了一种新的放射生物学模型来描述同一理论框架内两个致癌相关终点的剂量-反应曲线.利用具有代表性的实验数据验证了模型的一致性和有效性。拟合结果表明,与靶向效应(TE)和NTE模型相比，当前模型在处理由具有不同LET的多种类型IR引起的染色体畸变和肿瘤患病率的实验数据时具有更好的拟合能力。值得注意的是,本模型未引入NTE术语,足以描述低剂量区域IR诱导的染色体畸变和NTE的肿瘤患病率的剂量-反应曲线.根据拟合参数，计算了3个低剂量的LET依赖性RBE值.我们的结果表明，当前模型预测的RBE值随着染色体畸变和肿瘤患病率终点剂量的增加而逐渐降低。此外,还将计算出的RBE与其他模型评估的RBE进行了比较.这些分析表明，所提出的模型可以作为一种替代工具，很好地描述多个致癌相关终点的剂量反应曲线，并有效地估计低剂量区域的RBE。
