Butterworth Karl T, McMahon Stephen J, McKee Jamie C, Patel Gaurang, Ghita Mihaela, Cole Aidan J, McGarry Conor K, O'Sullivan Joe M, Hounsell Alan R, Prise Kevin M
a Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom;
d Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Radiat Res. 2015 Jun;183(6):656-64. doi: 10.1667/RR13992.1. Epub 2015 May 14.
Advanced radiotherapy techniques such as intensity-modulated radiation therapy (IMRT) achieve high levels of conformity to the target volume through the sequential delivery of highly spatially and temporally modulated radiation fields, which have been shown to impact radiobiological response. This study aimed to characterize the time and cell type dependency of survival responses to modulated fields using single cell type (SCT) and mixed cell type (MCT) co-culture models of transformed fibroblast (AG0-1522b) cells, prostate (DU-145) and lung (H460) cancer cells. In SCT cultures, in-field responses showed no significant time dependency while out-of-field responses occurred early, and plateaued 6 h after irradiation in both DU-145 and H460 cells. Under modulated beam configurations MCT co-cultures showed cell-specific, differential out-of-field responses depending on the irradiated in-field and responding out-of-field cell type. The observed differential out-of-field responses may be due to the genetic background of the cells, in particular p53 status, which has been shown to mediate radiation-induced bystander effects (RIBEs). These data provide further insight into the radiobiological parameters that influence out-of-field responses, which have potential implications for advanced radiotherapy modalities and may provide opportunities for biophysical optimization in radiotherapy treatment planning.
先进的放射治疗技术，如调强放射治疗（IMRT），通过顺序递送高度空间和时间调制的辐射野，实现了对靶区的高度适形，这些辐射野已被证明会影响放射生物学反应。本研究旨在使用转化成纤维细胞（AG0-1522b）、前列腺（DU-145）和肺癌（H460）细胞的单细胞类型（SCT）和混合细胞类型（MCT）共培养模型，来表征对调制野存活反应的时间和细胞类型依赖性。在SCT培养中，场内反应没有显示出明显的时间依赖性，而场外反应出现较早，并且在DU-145和H460细胞中照射后6小时达到平稳状态。在调制束配置下，MCT共培养显示出细胞特异性的、不同的场外反应，这取决于照射的场内和反应的场外细胞类型。观察到的不同场外反应可能是由于细胞的遗传背景，特别是p53状态，它已被证明可介导辐射诱导的旁观者效应（RIBE）。这些数据进一步深入了解了影响场外反应的放射生物学参数，这对先进的放射治疗模式具有潜在影响，并可能为放射治疗计划中的生物物理优化提供机会。
