Wang Hao, Li Jinna, Qu Ang, Liu Jingjia, Zhao Yong, Wang Junjie
Radiat Oncol. 2013 Aug 9;8:196. doi: 10.1186/1748-717X-8-196.
To determine the biological effectiveness of single, fractionated and continuous low dose rate irradiation on the human colorectal cancer cell line CL187 in vitro and explore the cellular mechanisms.
The CL187 cells were exposed to radiation of 6 MV X-ray at a high dose rate of 4Gy/min and 125I seed at a low dose rate of 2.77 cGy/h. Three groups were employed: single dose radiation group (SDR), fractionated dose radiation group (FDR) by 2Gy/f and continuous low dose rate radiation group (CLDR). Four radiation doses 2, 4, 6 and 8Gy were chosen and cells without irradiation as the control. The responses of CL187 cells to distinct modes of radiation were evaluated by the colony-forming assay, cell cycle progression as well as apoptosis analysis. In addition, we detected the expression patterns of DNA-PKcs, Ku70 and Ku80 by Western blotting.
The relative biological effect for 125I seeds compared with 6 MV X-ray was 1.42. 48 hrs after 4Gy irradiation, the difference between proportions of cells at G2/M phase of SDR and CLDR groups were statistically significant (p = 0.026), so as the FDR and CLDR groups (p = 0.005). 48 hrs after 4Gy irradiation, the early apoptotic rate of CLDR group was remarkably higher than SDR and FDR groups (CLDR vs. SDR, p = 0.001; CLDR vs. FDR, p = 0.02), whereas the late apoptotic rate of CLDR group increased significantly compared with SDR and FDR group (CLDR vs. SDR, p = 0.004; CLDR vs. FDR, p = 0.007). Moreover, DNA-PKcs and Ku70 expression levels in CLDR-treated cells decreased compared with SDR and FDR groups.
Compared with the X-ray high dose rate irradiation, 125I seeds CLDR showed more effective induction of cell apoptosis and G2/M cell cycle arrest. Furthermore, 125I seeds CLDR could impair the DNA repair capability by down-regulating DNA-PKcs and Ku70 expression.
确定单次、分次和连续低剂量率照射对人结肠癌细胞系CL187的体外生物学效应，并探讨其细胞机制。
将CL187细胞分别暴露于6MV X射线高剂量率4Gy/min照射和125I粒子低剂量率2.77cGy/h照射。分为三组：单次剂量照射组（SDR）、分次剂量照射组（FDR，2Gy/次）和连续低剂量率照射组（CLDR）。选择2、4、6和8Gy四个照射剂量，未照射细胞作为对照。通过集落形成试验、细胞周期进程以及凋亡分析评估CL187细胞对不同照射模式的反应。此外，通过蛋白质免疫印迹法检测DNA-PKcs、Ku70和Ku80的表达模式。
与6MV X射线相比，125I粒子的相对生物学效应为1.42。4Gy照射后48小时，SDR组与CLDR组G2/M期细胞比例差异有统计学意义（p = 0.026），FDR组与CLDR组差异也有统计学意义（p = 0.005）。4Gy照射后48小时，CLDR组早期凋亡率显著高于SDR组和FDR组（CLDR与SDR比较，p = 0.001；CLDR与FDR比较，p = 0.02），而CLDR组晚期凋亡率与SDR组和FDR组相比显著升高（CLDR与SDR比较，p = 0.004；CLDR与FDR比较，p = 0.007）。此外，与SDR组和FDR组相比，CLDR处理的细胞中DNA-PKcs和Ku70表达水平降低。
与X射线高剂量率照射相比，125I粒子CLDR更有效地诱导细胞凋亡和G2/M期细胞周期阻滞。此外，125I粒子CLDR可通过下调DNA-PKcs和Ku70表达损害DNA修复能力。
