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Comparison of signaling profiles in the low dose range following low and high LET radiation.
Life Sciences in Space Research ( IF 2.9 ) Pub Date : 2020-02-22 , DOI: 10.1016/j.lssr.2020.02.002
Deepa M Sridharan 1 , Lung-Chang Chien 2 , Francis A Cucinotta 3 , Janice M Pluth 3
Affiliation  

During space travel astronauts will be exposed to a very low, mixed field of radiation containing different high LET particles of varying energies, over an extended period. Thus, defining how human cells respond to these complex low dose exposures is important in ascertaining risk. In the current study, we have chosen to investigate how low doses of three different ion's at various energies uniquely change the kinetics of three different phospho-proteins. A normal hTERT immortalized fibroblast cell line, 82–6, was exposed to a range of lower doses (0.05–0.5 Gy) of radiation of different qualities and energies (Si 1000 MeV/u, Si 300 MeV/u, Si 173 MeV/u, Si 93 MeV/u, Fe 1000 MeV/u, Fe 600 MeV/u, Fe 300 MeV/u, Ti 300 MeV/u, Ti 326 MeV/u, Ti 386 MeV/u), covering a wide span of LET's. Exposed samples were analyzed for the average intensity of signal as a fold over the geometric mean level of the sham controls. Three phospho-proteins known to localize to DNA DSBs following radiation (γH2AX, pATF2, pSMC1) were studied. The kinetics of their response was quantified by flow cytometery at 2 and 24 h post exposure. These studies reveal unique kinetic patterns based on the ion, energy, fluence and time following exposure. In addition, γH2AX phosphorylation patterns are uniquely different from phospho-proteins known to be primarily phosphorylated by ATM. This latter finding suggests that the activating kinase(s), or the phosphatases deactivating these proteins, exhibit differences in their response to various radiation qualities and/ or doses of exposure. Further studies will be needed to better define what the differing kinetics for the kinases activated by the unique radiation qualities plays in the biological effectiveness of the particle.



中文翻译:

低和高LET辐射后低剂量范围内信号分布的比较。

在太空旅行期间,宇航员将长时间暴露在一个非常低的混合辐射场中,该辐射场包含具有不同能量的不同高LET粒子。因此,确定人类细胞如何应对这些复杂的低剂量暴露对于确定风险很重要。在当前的研究中,我们选择研究低剂量的三种不同离子在各种能量下如何独特地改变三种不同磷蛋白的动力学。正常的hTERT永生化成纤维细胞系82-6暴露于一系列不同质量和能量的较低剂量(0.05-0.5 Gy)的辐射下(Si 1000 MeV / u,Si 300 MeV / u,Si 173 MeV / u,Si 93 MeV / u,Fe 1000 MeV / u,Fe 600 MeV / u,Fe 300 MeV / u,Ti 300 MeV / u,Ti 326 MeV / u,Ti 386 MeV / u),涵盖了让我们。分析暴露的样品的平均信号强度,其为假对照的几何平均水平的倍数。研究了三种已知在辐射后定位于DNA DSB的磷酸蛋白(γH2AX,pATF2,pSMC1)。在暴露后2小时和24小时,通过流式细胞仪定量其反应的动力学。这些研究揭示了基于离子,能量,通量和暴露后时间的独特动力学模式。此外,γH2AX磷酸化模式与已知主要被ATM磷酸化的磷蛋白有独特的区别。后一个发现表明活化激酶或使这些蛋白质失活的磷酸酶在对各种辐射质量和/或剂量的反应中表现出差异。

更新日期:2020-02-22
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