二甲基亚砜对α、β和俄歇电子发射体（223）Ra、（188）Re 和（99m）Tc 诱导质粒 DNA 链断裂和 PC Cl3 哺乳动物细胞集落形成的影响。
The effect of dimethyl sulfoxide on the induction of DNA strand breaks in plasmid DNA and colony formation of PC Cl3 mammalian cells by alpha-, beta-, and Auger electron emitters (223)Ra, (188)Re, and (99m)Tc.
机构信息
Department of Nuclear Medicine, University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, D-01307, Dresden, Germany.
出版信息
EJNMMI Res. 2016 Dec;6(1):48. doi: 10.1186/s13550-016-0203-x. Epub 2016 Jun 3.
BACKGROUND
DNA damage occurs as a consequence of both direct and indirect effects of ionizing radiation. The severity of DNA damage depends on the physical characteristics of the radiation quality, e.g., the linear energy transfer (LET). There are still contrary findings regarding direct or indirect interactions of high-LET emitters with DNA. Our aim is to determine DNA damage and the effect on cellular survival induced by (223)Ra compared to (188)Re and (99m)Tc modulated by the radical scavenger dimethyl sulfoxide (DMSO).
METHODS
Radioactive solutions of (223)Ra, (188)Re, or (99m)Tc were added to either plasmid DNA or to PC Cl3 cells in the absence or presence of DMSO. Following irradiation, single strand breaks (SSB) and double strand breaks (DSB) in plasmid DNA were analyzed by gel electrophoresis. To determine the radiosensitivity of the rat thyroid cell line (PC Cl3), survival curves were performed using the colony formation assay.
RESULTS
Exposure to 120 Gy of (223)Ra, (188)Re, or (99m)Tc leads to maximal yields of SSB (80 %) in plasmid DNA. Irradiation with 540 Gy (223)Ra and 500 Gy (188)Re or (99m)Tc induced 40, 28, and 64 % linear plasmid conformations, respectively. DMSO prevented the SSB and DSB in a similar way for all radionuclides. However, with the α-emitter (223)Ra, a low level of DSB could not be prevented by DMSO. Irradiation of PC Cl3 cells with (223)Ra, (188)Re, and (99m)Tc pre-incubated with DMSO revealed enhanced survival fractions (SF) in comparison to treatment without DMSO. Protection factors (PF) were calculated using the fitted survival curves. These factors are 1.23 ± 0.04, 1.20 ± 0.19, and 1.34 ± 0.05 for (223)Ra, (188)Re, and (99m)Tc, respectively.
CONCLUSIONS
For (223)Ra, as well as for (188)Re and (99m)Tc, dose-dependent radiation effects were found applicable for plasmid DNA and PC Cl3 cells. The radioprotection by DMSO was in the same range for high- and low-LET emitter. Overall, the results indicate the contribution of mainly indirect radiation effects for each of the radionuclides regarding DNA damage and cell survival. In summary, our findings may contribute to fundamental knowledge about the α-particle induced DNA damage.
背景
DNA 损伤是电离辐射的直接和间接效应的结果。DNA 损伤的严重程度取决于辐射质量的物理特性，例如线性能量转移（LET）。关于高 LET 发射器与 DNA 的直接或间接相互作用仍存在相反的发现。我们的目的是确定与（188）Re 和（99m）Tc 相比，（223）Ra 引起的 DNA 损伤及其对细胞存活的影响，并通过自由基清除剂二甲亚砜（DMSO）进行调节。
方法
将放射性（223）Ra、（188）Re 或（99m）Tc 溶液加入质粒 DNA 或无或有 DMSO 的 PC Cl3 细胞中。照射后，通过凝胶电泳分析质粒 DNA 中的单链断裂（SSB）和双链断裂（DSB）。为了确定大鼠甲状腺细胞系（PC Cl3）的放射敏感性，使用集落形成测定法进行生存曲线实验。
结果
暴露于 120Gy 的（223）Ra、（188）Re 或（99m）Tc 导致质粒 DNA 中 SSB 的最大产量为 80%。用 540Gy（223）Ra 和 500Gy（188）Re 或（99m）Tc 照射可分别诱导 40%、28%和 64%的线性质粒构象。DMSO 以相似的方式防止所有放射性核素的 SSB 和 DSB。然而，对于α发射器（223）Ra，DMSO 无法防止低水平的 DSB。用（223）Ra、（188）Re 和（99m）Tc 预先孵育的 PC Cl3 细胞照射 DMSO 显示与无 DMSO 处理相比，存活分数（SF）提高。使用拟合的生存曲线计算保护因子（PF）。这些因子分别为（223）Ra、（188）Re 和（99m）Tc 的 1.23±0.04、1.20±0.19 和 1.34±0.05。
结论
对于（223）Ra 以及（188）Re 和（99m）Tc，发现剂量依赖性辐射效应适用于质粒 DNA 和 PC Cl3 细胞。DMSO 的放射防护作用在高 LET 和低 LET 发射器之间相同。总的来说，结果表明，对于每种放射性核素的 DNA 损伤和细胞存活，主要是间接辐射效应的贡献。综上所述，我们的研究结果可能有助于对α粒子诱导的 DNA 损伤的基本认识。
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