a University of Melbourne, Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville 3052, Australia.
b Epworth Radiation Oncology, Epworth HealthCare, Richmond 3121, Australia.
Radiat Res. 2018 Feb;189(2):146-155. doi: 10.1667/RR4633.1.
Synchrotron microbeam radiation therapy is a promising preclinical radiotherapy modality that has been proposed as an alternative to conventional radiation therapy for diseases such as diffuse intrinsic pontine glioma (DIPG), a devastating pediatric tumor of the brainstem. The primary goal of this study was to characterize and compare the radiosensitivity of two DIPG cell lines (SF7761 and JHH-DIPG-1) to microbeam and conventional radiation. We hypothesized that these DIPG cell lines would exhibit differential responses to each radiation modality. Single cell suspensions were exposed to microbeam (112, 250, 560, 1,180 Gy peak dose) or conventional (2, 4, 6 and 8 Gy) radiation to produce clonogenic cell-survival curves. Apoptosis induction and the cell cycle were also analyzed five days postirradiation using flow cytometry. JHH-DIPG-1 cells displayed greater radioresistance than SF7761 to both microbeam and conventional radiation, with higher colony formation and increased accumulation of G/M-phase cells. Apoptosis was significantly increased in SF7761 cells compared to JHH-DIPG-1 after microbeam irradiation, demonstrating cell-line specific differential radiosensitivity to microbeam radiation. Additionally, biologically equivalent doses to microbeam and conventional radiation were calculated based on clonogenic survival, furthering our understanding of the response of cancer cells to these two radiotherapy modalities.
同步辐射微束放射治疗是一种有前途的临床前放射治疗方式,它被提议作为弥漫性内生脑桥胶质瘤(DIPG)等疾病的常规放射治疗的替代方法,DIPG 是一种毁灭性的脑干儿童肿瘤。本研究的主要目的是表征和比较两种 DIPG 细胞系(SF7761 和 JHH-DIPG-1)对微束和常规放射的敏感性。我们假设这些 DIPG 细胞系对每种放射方式会表现出不同的反应。单细胞悬液暴露于微束(112、250、560、1180Gy 峰值剂量)或常规(2、4、6 和 8Gy)辐射下,以产生克隆形成细胞存活曲线。在辐照后五天,还使用流式细胞术分析了细胞凋亡诱导和细胞周期。与 SF7761 相比,JHH-DIPG-1 细胞对微束和常规放射均具有更高的放射抗性,其集落形成率更高,G/M 期细胞的积累增加。与 JHH-DIPG-1 相比,SF7761 细胞在微束照射后细胞凋亡明显增加,表明细胞系对微束辐射的放射敏感性存在差异。此外,根据克隆形成存活计算了微束和常规放射的等效生物学剂量,进一步了解了癌细胞对这两种放射治疗方式的反应。