Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):250-6. doi: 10.1016/j.ijrobp.2011.10.058. Epub 2012 Jan 26.
To develop a model to describe the response of cell populations to spatially modulated radiation exposures of relevance to advanced radiotherapies.
A Monte Carlo model of cellular radiation response was developed. This model incorporated damage from both direct radiation and intercellular communication including bystander signaling. The predictions of this model were compared to previously measured survival curves for a normal human fibroblast line (AGO1522) and prostate tumor cells (DU145) exposed to spatially modulated fields.
The model was found to be able to accurately reproduce cell survival both in populations which were directly exposed to radiation and those which were outside the primary treatment field. The model predicts that the bystander effect makes a significant contribution to cell killing even in uniformly irradiated cells. The bystander effect contribution varies strongly with dose, falling from a high of 80% at low doses to 25% and 50% at 4 Gy for AGO1522 and DU145 cells, respectively. This was verified using the inducible nitric oxide synthase inhibitor aminoguanidine to inhibit the bystander effect in cells exposed to different doses, which showed significantly larger reductions in cell killing at lower doses.
The model presented in this work accurately reproduces cell survival following modulated radiation exposures, both in and out of the primary treatment field, by incorporating a bystander component. In addition, the model suggests that the bystander effect is responsible for a significant portion of cell killing in uniformly irradiated cells, 50% and 70% at doses of 2 Gy in AGO1522 and DU145 cells, respectively. This description is a significant departure from accepted radiobiological models and may have a significant impact on optimization of treatment planning approaches if proven to be applicable in vivo.
开发一种模型，以描述与先进放射疗法相关的空间调制辐射暴露对细胞群体的反应。
开发了一种细胞辐射反应的蒙特卡罗模型。该模型将直接辐射和细胞间通讯（包括旁观者信号）造成的损伤都纳入其中。将该模型的预测与先前测量的正常人类成纤维细胞系（AGO1522）和前列腺肿瘤细胞（DU145）暴露于空间调制场后的存活曲线进行了比较。
发现该模型能够准确地重现直接暴露于辐射的细胞群体和处于初级治疗场之外的细胞群体的细胞存活情况。该模型预测，即使在均匀照射的细胞中，旁观者效应也会对细胞杀伤产生重大贡献。旁观者效应的贡献随剂量强烈变化，从低剂量时的 80%高峰降至 AGO1522 和 DU145 细胞的 4 Gy 时的 25%和 50%。使用诱导型一氧化氮合酶抑制剂氨基胍抑制不同剂量下暴露细胞的旁观者效应进行了验证，结果表明在较低剂量下细胞杀伤明显减少。
本研究提出的模型通过纳入旁观者成分，准确地再现了调制辐射暴露后处于初级治疗场内外的细胞存活情况。此外，该模型表明，旁观者效应是均匀照射细胞中细胞杀伤的重要部分，在 AGO1522 和 DU145 细胞中分别占 2 Gy 剂量的 50%和 70%。这种描述与公认的放射生物学模型有很大的不同，如果在体内证明是适用的，可能会对治疗计划方法的优化产生重大影响。
