The different biological effects of single, fractionated and continuous low dose rate irradiation on CL187 colorectal cancer cells.

The different biological effects of single, fractionated and continuous low dose rate irradiation on CL187 colorectal cancer cells.
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单次、分次和连续低剂量率照射对CL187结直肠癌细胞的不同生物学效应

DOI:
10.1186/1748-717x-8-196
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发表时间:
2013-08-09
期刊:
Radiation oncology (London, England)
影响因子:
--
通讯作者:
Wang J
Wang J
中科院分区:
其他
文献类型:
--
作者:
Wang H;Li J;Qu A;Liu J;Zhao Y;Wang J

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目的探讨单次、分次和连续低剂量率照射对体外培养的人结肠癌细胞株CL187的生物学效应,并探讨其作用机制。材料与方法将人结肠癌细胞株CL187分为单剂量照射组(SDR)、分次照射组(FDR)和连续低剂量率照射组(CLDR),照射剂量分别为6 MVX射线和125I粒子,照射剂量分别为4Gy/min和2.77cGyh。选择2、4、6、8Gy4个照射剂量,未照射的细胞作为对照。通过集落形成实验、细胞周期进程和细胞凋亡分析,评价CL187细胞对不同辐射方式的反应。通过Western blotting检测DNA-PKcs、Ku70和Ku80的表达模式。结果125I种子与6 MV X射线照射的相对生物学效应为1.42。照射后48hSDR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G2/M期细胞比例差异有统计学意义(p = 0.005)。照射后48hCLDR组早期凋亡率显著高于SDR组和FDR组(p = 0.001;CLDRvs.FDR,p = 0.02),晚期凋亡率显著高于SDR组和FDR组(p = 0.004;CLDRvs.FDR,p = 0.007)。CLDR组细胞DNA-PKcs和Ku70的表达水平低于SDR组和FDR组。结论与X射线高剂量率照射相比,125I籽粒CLDR能更有效地诱导细胞凋亡和G2/M期细胞周期停滞。此外,125I种子CLDR可通过下调DNA-PKcs和Ku70的表达来损害DNA修复能力。
PurposeTo 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.Materials and methodsThe CL187 cells were exposed to radiation of 6 MV X-ray at a high dose rate of 4Gy/min and125I 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.ResultsThe relative biological effect for125I 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.ConclusionsCompared 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.