Jones T D, Morris M D, Young R W
Health and Safety Research Division, Oak Ridge National Laboratory, Tennessee 37831-6101.
Radiat Res. 1991 Dec;128(3):258-66.
A model for damage, repair, killing, and repopulation of myelopoietic marrow is presented. Evaluation produces time and dose-rate profiles during and following any complex irradiation. Equations model variable dose rates, multiple exposures, different sources, and arbitrary intervals between treatments. If factors which dominate the control of biological processes can be demonstrated, an option is to set biological rate constants to experimentally determined values. Previously, knowledge did not permit identification of dominating biological processes and their temporal rates. But a unique feature of this study is that unspecified lesions for killing and injury of cells are evaluated from mortality data on the animal species of choice. "Unspecified" is used to indicate a condition of assumption-free modeling of molecular processes, whereby rate constants for cellular effects are simply computed directly from animal mortality data. Coefficients (estimated by maximum-likelihood methods for nonspecific processes) are compared with experimental values for specific processes. The model has many uses, including modeling of the myelopoietic potential as a function of time. Another option is to calculate the whole-body survival curve for cells that control myelopoiesis as a result of the treatment schedule. Also through simple extensions of the model, an extremely complex protocol can be identified with an equivalent prompt dose value--even for partial-body, fractionated exposures.
本文提出了一种骨髓造血损伤、修复、杀伤和再增殖的模型。该评估可得出任何复杂照射期间及之后的时间和剂量率曲线。方程可模拟可变剂量率、多次照射、不同源以及治疗之间的任意时间间隔。如果能够证明主导生物过程控制的因素，那么一种选择是将生物速率常数设定为实验确定的值。以前，由于缺乏相关知识，无法确定主导生物过程及其时间速率。但本研究的一个独特之处在于，从所选动物物种的死亡率数据中评估细胞杀伤和损伤的未明确病变。“未明确”用于表示分子过程的无假设建模情况，即细胞效应的速率常数直接从动物死亡率数据简单计算得出。将（通过最大似然法估计的非特异性过程的）系数与特定过程的实验值进行比较。该模型有许多用途，包括将骨髓造血潜能作为时间函数进行建模。另一种选择是根据治疗方案计算控制骨髓造血的细胞的全身存活曲线。此外，通过对模型进行简单扩展，即使对于局部身体、分次照射，也可以用等效的即时剂量值确定极其复杂的方案。
