The radiobiological effectiveness of carbon-ion beams on growing neurons

The radiobiological effectiveness of carbon-ion beams on growing neurons
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DOI:
10.1080/09553000903020032
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发表时间:
2009-01-01
影响因子:
2.6
通讯作者:
Nakano,Takashi
Nakano,Takashi
中科院分区:
医学3区
文献类型:
--
作者:
Al-Jahdari,Wael S.;Suzuki,Yoshiyuki;Nakano,Takashi

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目的:近年来,碳离子束被报道对控制多种癌症效果显著,且毒性较小,被认为是一种很有前途的癌症治疗方法。然而,碳离子束对正常神经元的生物学效应尚不清楚。因此,本研究从形态和功能两个方面研究了碳离子对神经元的影响。材料和方法:从第8天和第16天鸡胚胎分离背根神经节(DRG)和交感神经节链(SYP),培养20h,用碳离子束和X射线照射培养的神经元。用生长锥体塌陷(GCC)法、末端脱氧核苷酸转移酶(TdT)介导的脱氧尿苷三磷酸缺口末端标记法(TUNEL)和4-[3-(4-碘苯基)-2-(4-硝基苯基)-2H-5-四氮苯]-1,3-苯二磺酸[WST-1]分别检测细胞的形态变化、细胞凋亡率和细胞存活率。结果:辐射对GCC细胞和突起的破坏呈时间和辐射剂量依赖性。两种照射后细胞形态特征的变化相似。形态和功能分析显示,第8天神经元的放射敏感性高于第16天神经元,而背根神经节的放射敏感性与SYMP相当。GCC和TUNEL标记指数的剂量-效应曲线显示,较高的相对生物效应值与较低的致死剂量(LD)值相关,而较低的相对生物效应值与较高的LD值相关。结论:高线性能量转移(LET)照射比低LET照射更有效地诱导早期发育的神经细胞GCC和细胞凋亡。GCC是一种可靠的评估神经元放射生物学反应的方法。
Purpose:Recently carbon-ion beams have been reported to be remarkably effective for controlling various cancers with less toxicity and are thought to be a promising modality for cancer treatment. However, the biological effect of carbon-ion beams arising on normal neuron remains unknown. Therefore, this study was undertaken to investigate the effect of carbon-ion beams on neurons by using both morphological and functional assays.Materials and methods:Dorsal root ganglia (DRG) and sympathetic ganglion chains (SYMP) were isolated from day-8 and day-16 chick embryos and cultured for 20 h. Cultured neurons were exposed to carbon-ion beams and X-rays. Morphological changes, apoptosis and cell viability were evaluated with the Growth Cone Collapse (GCC), Terminal deoxynucleotidyl Transferase (TdT)-mediated deoxyUridine TriPhosphate (dUTP) nick End Labeling [TUNEL] assay and 4-[3-(4-iodophenyl)- 2-(4-nitrophenyl)- 2H-5-tetrazolio]- 1,3-benzenedisulfonate [WST-1] assays, respectively.Results:Irradiation caused GCC and neurite destruction on a time- and irradiation dose-dependent manner. Changes in morphological characteristics were similar following either irradiation. Morphological and functional assays showed that day-8 neurons were more radiosensitive than day-16 neurons, whereas, radiosensitivity of DRG was comparable to that of SYMP. The dose-response fitting curve utilising both GCC and TUNEL labeling index showed higher relative biological effectiveness (RBE) values were associated with lower lethal dose (LD) values, while lower RBE was associated with higher LD values.Conclusion:Exposure to high-linear energy transfer (LET) irradiation is up to 3.2 more efficient to induce GCC and apoptosis, in early developed neuronal cells, than low-LET irradiation. GCC is a reliable method to assess the radiobiological response of neurons.