标题： 基底细胞增生在克隆扩增与氡浓度关系中的潜在作用的定量分析 显示英文标题

标题： Quantitative analysis of the potential role of basal cell hyperplasia in the relationship between clonal expansion and radon concentration

摘要： 应用两阶段克隆扩展模型于铀矿工人肺癌流行病学中，已揭示出氡作为促进剂，有助于已发生突变细胞的克隆扩展。 克隆扩展率随氡浓度非线性增加，在一定暴露率以上呈现平台期。 其潜在机制尚不清楚。 早前我们提出，慢性氡暴露可能引发祖细胞增生。 本研究的目的是检验增生的诱导是否可为克隆扩展率的平台期提供定量解释。 为此，准备了具有不同数量基底细胞的数值上皮模型。 细胞核击中数通过自开发的蒙特卡罗代码计算得出。 根据细胞核击中数估算存活分数。 假设细胞死亡与细胞分裂之间处于平衡状态，计算细胞分裂率。 还假设克隆扩展率与细胞分裂率成正比，因此细胞分裂率和克隆扩展率的相对增加是暴露率的相同函数。 虽然模拟结果高度依赖于具有高不确定性的模型参数，但已找到一个参数集，使得细胞分裂率与暴露率的关系对应于克隆扩展率的平台期。 然而，由于所用参数的不确定性很高，需要进一步研究以确定增生的诱导是否负责克隆扩展率的非线性增加。 尽管如此，本研究展示了计算建模如何有助于观察性和实验性辐射防护研究的整合。 显示英文摘要

摘要： Applying the two-stage clonal expansion model to epidemiology of lung cancer among uranium miners, it has been revealed that radon acts as a promoting agent facilitating the clonal expansion of already mutated cells. Clonal expansion rate increases non-linearly by radon concentration showing a plateau above a given exposure rate. The underlying mechanisms remain unclear. Earlier we proposed that progenitor cell hyperplasia may be induced upon chronic radon exposure. The objective of the present study is to test whether the induction of hyperplasia may provide a quantitative explanation for the plateau in clonal expansion rate. For this purpose, numerical epithelium models were prepared with different number of basal cells. Cell nucleus hits were computed by an own-developed Monte-Carlo code. Surviving fractions were estimated based on the number of cell nucleus hits. Cell division rate was computed supposing equilibrium between cell death and cell division. It was also supposed that clonal expansion rate is proportional to cell division rate, and therefore the relative increase in cell division rate and clonal expansion rate are the same functions of exposure rate. While the simulation results highly depend on model parameters with high uncertainty, a parameter set has been found resulting in a cell division rate exposure rate relationship corresponding to the plateau in clonal expansion rate. Due to the high uncertainty of the applied parameters, however, further studies are required to decide whether the induction of hyperplasia is responsible for the non-linear increase in clonal expansion rate or not. Nevertheless the present study exemplifies how computational modelling can contribute to the integration of observational and experimental radiation protection research.