Nikjoo Hooshang, Khvostunov Igor K
MRC Radiation & Genome Stability Unit, Harwell OX11 0RD, UK.
Int J Radiat Biol. 2003 Jan;79(1):43-52.
To construct a quantitative model of the radiation-induced bystander effect based on diffusion-type spreading of bystander signal communication between the hit and non-hit cells. Cell inactivation and induced oncogenic transformation by broad- and microbeam irradiation systems are considered.
The biophysical model ByStander Diffusion Modelling (BSDM) postulates that the oncogenic bystander response observed in non-hit cells originates from specific signals received from inactivated cells. The bystander signals are assumed to be protein-like molecules spreading in the culture media by Brownian motion. The bystander signals are assumed to switch cells into a state of cell death (apoptotic/mitotic/necrosis) or induced oncogenic transformation modes.
The bystander cell survival observed after treatment with the irradiated conditioned medium (ICM) using the broad-beam and the microbeam irradiation modalities were analysed and interpreted in the framework of the BSDM model. The model predictions for cell inactivation and induced oncogenic transformation frequencies agree well with observed data from micro and broad-beam experiments. In the case of irradiation with constant fraction of cells, transformation frequency for the bystander effect increases with increasing radiation dose.
Bystander modelling based on diffusion of signals is in good agreement with experimental cell survival data and induced oncogenic transformation frequencies. The data confirm the protein-like nature of the bystander signal. Linear extrapolation of the cell response to low doses of radiation might underestimate carcinogenic risk, for example for domestic radon hazards, if the contribution from the bystander effect is neglected. The BSDM predicts that the bystander effect cannot be interpreted solely as a low-dose effect phenomenon. It is shown that the bystander component of radiation response can increase with dose and be observed at high doses as well as at low doses. The validity of this conclusion is supported by analysis of experimental results from high-linear energy transfer microbeam experiments.
基于命中细胞与未命中细胞间旁观者信号通信的扩散型传播构建辐射诱导旁观者效应的定量模型。考虑了宽束和微束照射系统导致的细胞失活及诱导的致癌转化。
生物物理模型“旁观者扩散建模（BSDM）”假定，在未命中细胞中观察到的致癌旁观者反应源自从失活细胞接收的特定信号。旁观者信号被假定为通过布朗运动在培养基中扩散的类蛋白质分子。旁观者信号被假定将细胞转变为细胞死亡（凋亡/有丝分裂/坏死）状态或诱导致癌转化模式。
在BSDM模型框架内分析并解释了使用宽束和微束照射方式用辐照条件培养基（ICM）处理后观察到的旁观者细胞存活情况。该模型对细胞失活和诱导致癌转化频率的预测与微束和宽束实验的观察数据吻合良好。在恒定细胞比例照射的情况下，旁观者效应的转化频率随辐射剂量增加而增加。
基于信号扩散的旁观者建模与实验细胞存活数据及诱导致癌转化频率吻合良好。数据证实了旁观者信号的类蛋白质性质。如果忽略旁观者效应的贡献，将细胞反应线性外推至低剂量辐射可能会低估致癌风险，例如对于家庭氡危害。BSDM预测，旁观者效应不能仅被解释为低剂量效应现象。结果表明，辐射反应的旁观者成分可随剂量增加，在高剂量以及低剂量下均可观察到。对高线性能量转移微束实验结果的分析支持了这一结论的有效性。
