Nuclear & Radiological Engineering and Medical Physics Program, Georgia Institute of Technology, 900 Atlantic Drive, Atlanta, GA 30332-0425, USA.
Mutat Res. 2010 Apr-Jun;704(1-3):175-81. doi: 10.1016/j.mrrev.2010.02.001. Epub 2010 Feb 21.
Radiobiological models are used in modern radiotherapy to evaluate the biological effects of different treatment plans or modalities. A radiobiological model typically converts a physical quantity (e.g. absorbed dose) to a biological quantity (e.g. cell survival fraction). Currently, the linear-quadratic model (LQM) is the most widely used model. Since it is a deterministic model, the LQM naturally ignores the uncertainties arising from the stochastic randomness of energy depositions along radiation tracks and the inherent unpredictable nature of biological systems. Recently, many studies have revealed the detailed spatial and temporal distributions of DNA damages, e.g. the DNA double strand breaks (DSBs), along various types of radiation tracks traversing a cell nucleus. Studies have also been conducted to unravel the biological pathways that involve in how cells and tissues process DNA damages. As such, the author proposes to start developing a new multi-scale radiobiological model based on the "bottom-up" approach. The model includes a Monte Carlo procedure to treat the stochastic randomness of radiation-induced DNA damages, and it also includes the relevant intercellular and intracellular pathways to allow the DNA damages to evolve into higher-order biological endpoints, e.g. chromosome aberrations, cell death, or tumorigenesis. Because of its stochastic nature, the new model inherently addresses the uncertainty issue being ignored by LQM. More importantly perhaps is that the model opens a new way to study radiation effects that involve biological pathways, and therefore, may have a profound impact on radiotherapy in the future.
放射生物学模型用于现代放射治疗中，以评估不同治疗计划或方式的生物学效应。放射生物学模型通常将物理量（例如吸收剂量）转换为生物学量（例如细胞存活分数）。目前，线性二次模型（LQM）是最广泛使用的模型。由于它是确定性模型，LQM 自然忽略了沿辐射轨迹的能量沉积的随机性以及生物系统固有的不可预测性所带来的不确定性。最近，许多研究揭示了 DNA 损伤的详细时空分布，例如沿穿过细胞核的各种类型的辐射轨迹的 DNA 双链断裂（DSBs）。研究还揭示了涉及细胞和组织如何处理 DNA 损伤的生物学途径。因此，作者提出基于“自下而上”方法开始开发新的多尺度放射生物学模型。该模型包括一个蒙特卡罗程序来处理辐射诱导的 DNA 损伤的随机性，并且还包括相关的细胞间和细胞内途径，以使 DNA 损伤演变成更高阶的生物学终点，例如染色体畸变、细胞死亡或肿瘤发生。由于其随机性，新模型固有地解决了 LQM 忽略的不确定性问题。也许更重要的是，该模型为研究涉及生物学途径的辐射效应开辟了新途径，因此可能对未来的放射治疗产生深远影响。
