A theoretical approach to the role and critical issues associated with bystander effect in risk estimation
A theoretical approach to the role and critical issues associated with bystander effect in risk estimation
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DOI：
10.1191/0960327104ht422oa
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发表时间：
2004-02-01
影响因子：
2.8
通讯作者：
Khvostunov, IK
中科院分区：
文献类型：
--
作者：
Nikjoo, H;Khvostunov, IK
本文提出了一个辐射诱导旁观者效应的定量生物物理模型。旁观者模型的主要目的是确定旁观者信号是否可以与受体细胞周围培养基中通过扩散型过程传递的低分子量因子相关。细胞失活和诱导的致癌转化的微束和宽束照射系统被认为是。生物物理模型假设，在非命中细胞中观察到的致癌旁观者反应起源于从失活细胞接收的特异性信号。旁观者信号被假定为通过布朗运动在培养基中扩散的蛋白质样分子。假设旁观者信号将细胞切换到细胞死亡状态（凋亡/有丝分裂/坏死）或诱导致癌转化模式。在旁观者扩散模型（BSDM）的框架中分析和解释了使用宽束和微束照射方式用照射的条件培养基处理后观察到的旁观者细胞存活。模型预测的细胞失活和诱导的致癌转化频率同意从微束和宽束实验观察到的数据。在照射的情况下，与恒定比例的细胞，旁观者效应的转化频率增加，随着辐射剂量的增加。BSDM预测，旁观者效应不能仅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而增加，并可在高剂量和低剂量下观察到。高LET微束实验结果的分析支持了这一结论的有效性。
This paper presents a quantitative biophysical model of the radiation-induced bystander effect. The principle aim of the bystander model is to establish whether bystander signal can be associated with low molecular weight factors that are transmitted by diffusion type processes in the medium surrounding the recipient cells. Cell inactivation and induced oncogenic transformation by microbeam and broadbeam irradiation systems were considered. The biophysical model 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 using broadbeam and the microbeam irradiation modalities were analysed and interpreted in the framework of the Bystander Diffusion Model (BSDM). The model predictions for cell inactivation and induced oncogenic transformation frequencies agree well with observed data from microbeam and broadbeam experiments. In the case of irradiation with constant fraction of cells, transformation frequency for the bystander effect increases with increasing radiation dose. 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 can be observed at high doses as well as low doses. The validity of this conclusion is supported by analysis of experimental results from high-LET microbeam experiments.