Schöllnberger H, Mitchel R E J, Redpath J L, Crawford-Brown D J, Hofmann W
Department of Materials Engineering and Physics and Biophysics, University of Salzburg, Salzburg, Austria.
Radiat Res. 2007 Nov;168(5):614-26. doi: 10.1667/rr0742.1.
This work integrates two important cellular responses to low doses, detrimental bystander effects and apoptosis-mediated protective bystander effects, into a multistage model for chromosome aberrations and in vitro neoplastic transformation: the State-Vector Model. The new models were tested on representative data sets that show supralinear or U-shaped dose responses. The original model without the new low-dose features was also tested for consistency with LNT-shaped dose responses. Reductions of in vitro neoplastic transformation frequencies below the spontaneous level have been reported after exposure of cells to low doses of low-LET radiation. In the current study, this protective effect is explained with bystander-induced apoptosis. An important data set that shows a low-dose detrimental bystander effect for chromosome aberrations was successfully fitted by additional terms within the cell initiation stage. It was found that this approach is equivalent to bystander-induced clonal expansion of initiated cells. This study is an important step toward a comprehensive model that contains all essential biological mechanisms that can influence dose-response curves at low doses.
这项工作将细胞对低剂量的两种重要反应——有害旁观者效应和凋亡介导的保护性旁观者效应——整合到一个用于染色体畸变和体外肿瘤转化的多阶段模型：状态向量模型中。新模型在显示超线性或U形剂量反应的代表性数据集上进行了测试。没有新的低剂量特征的原始模型也针对与线性无阈（LNT）形剂量反应的一致性进行了测试。有报道称，细胞暴露于低剂量低传能线密度（LET）辐射后，体外肿瘤转化频率降低至自发水平以下。在当前研究中，这种保护作用是由旁观者诱导的凋亡来解释的。一个显示染色体畸变存在低剂量有害旁观者效应的重要数据集通过细胞起始阶段的附加项成功拟合。结果发现，这种方法等同于旁观者诱导的起始细胞克隆扩增。这项研究朝着一个全面模型迈出了重要一步，该模型包含了所有能够影响低剂量下剂量反应曲线的基本生物学机制。
