Dokic Ivana, Niklas Martin, Zimmermann Ferdinand, Mairani Andrea, Seidel Philipp, Krunic Damir, Jäkel Oliver, Debus Jürgen, Greilich Steffen, Abdollahi Amir
German Cancer Consortium, Translational Radiation Oncology, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg University Medical School , Heidelberg , Germany ; Heidelberg Ion Therapy Center , Heidelberg , Germany ; Heidelberg Institute of Radiation Oncology, National Center for Radiation Research in Oncology , Heidelberg , Germany.
Heidelberg Ion Therapy Center , Heidelberg , Germany ; National Center for Oncological Hadrontherapy , Pavia , Italy.
Front Oncol. 2015 Dec 7;5:275. doi: 10.3389/fonc.2015.00275. eCollection 2015.
Development of novel approaches linking the physical characteristics of particles with biological responses are of high relevance for the field of particle therapy. In radiobiology, the clonogenic survival of cells is considered the gold standard assay for the assessment of cellular sensitivity to ionizing radiation. Toward further development of next generation biodosimeters in particle therapy, cell-fluorescent ion track hybrid detector (Cell-FIT-HD) was recently engineered by our group and successfully employed to study physical particle track information in correlation with irradiation-induced DNA damage in cell nuclei. In this work, we investigated the feasibility of Cell-FIT-HD as a tool to study the effects of clinical beams on cellular clonogenic survival. Tumor cells were grown on the fluorescent nuclear track detector as cell culture, mimicking the standard procedures for clonogenic assay. Cell-FIT-HD was used to detect the spatial distribution of particle tracks within colony-initiating cells. The physical data were associated with radiation-induced foci as surrogates for DNA double-strand breaks, the hallmark of radiation-induced cell lethality. Long-term cell fate was monitored to determine the ability of cells to form colonies. We report the first successful detection of particle traversal within colony-initiating cells at subcellular resolution using Cell-FIT-HD.
开发将粒子的物理特性与生物反应联系起来的新方法对粒子治疗领域具有高度相关性。在放射生物学中,细胞的克隆形成存活率被认为是评估细胞对电离辐射敏感性的金标准检测方法。为了进一步开发粒子治疗中的下一代生物剂量计,我们团队最近设计了细胞荧光离子径迹混合探测器(Cell-FIT-HD),并成功用于研究与细胞核中辐射诱导的DNA损伤相关的物理粒子径迹信息。在这项工作中,我们研究了Cell-FIT-HD作为研究临床束流对细胞克隆形成存活率影响的工具的可行性。肿瘤细胞在荧光核径迹探测器上作为细胞培养物生长,模拟克隆形成试验的标准程序。Cell-FIT-HD用于检测集落起始细胞内粒子径迹的空间分布。物理数据与作为DNA双链断裂替代物的辐射诱导灶相关联,DNA双链断裂是辐射诱导细胞致死的标志。监测长期细胞命运以确定细胞形成集落的能力。我们报告了首次使用Cell-FIT-HD在亚细胞分辨率下成功检测集落起始细胞内的粒子穿越情况。