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DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure.
Radiation and Environmental Biophysics ( IF 1.7 ) Pub Date : 2020-01-02 , DOI: 10.1007/s00411-019-00825-x
Qi Wang 1 , Monica Pujol-Canadell 1 , Maria Taveras 1 , Guy Garty 1 , Jay Perrier 1 , Carlos Bueno-Beti 1 , Igor Shuryak 1 , David J Brenner 1 , Helen C Turner 1
Affiliation  

Environmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident or improvised nuclear device, and highlights the need to develop biological assays for low-dose rate, internal emitter radiation. To mimic low-dose rates attributable to fallout, we have developed a VAriable Dose-rate External 137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low-dose rate irradiations in the range of 0.1–1.2 Gy/day, while circumventing the complexities of dealing with radioactively contaminated biomaterials. We investigated the kinetics of mouse peripheral leukocytes DNA damage response in vivo after variable, low-dose rate 137Cs exposure. C57BL/6 mice were placed in the VADER over 7 days with total accumulated dose up to 2.7 Gy. Peripheral blood response including the leukocyte depletion, apoptosis as well as its signal protein p53 and DNA repair biomarker γ-H2AX was measured. The results illustrated that blood leukocyte numbers had significantly dropped by day 7. P53 levels peaked at day 2 (total dose = 0.91 Gy) and then declined; whereas, γ-H2AX fluorescence intensity (MFI) and foci number generally increased with accumulated dose and peaked at day 5 (total dose = 2.08 Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2 Gy and ≥ 2 Gy, highlighting the potential of γ-H2AX MFI as a biomarker for dosimetry in a protracted, environmental exposure scenario.



中文翻译:

可变的低剂量剂量暴露后,体内小鼠外周血白细胞的DNA损伤反应。

环境污染和放射性核素铯137(137 Cs)的摄入是核反应堆事故或简易核装置坠落所引起的重大问题,并突出显示了需要针对低剂量率内部发射极辐射开展生物测定的需求。为了模拟可归因于辐射的低剂量率,我们开发了一种可变剂量率外部137 Cs辐照仪(VADER),它可以提供范围在0.1-1.2 Gy /天的任意变化的渐进式低剂量率辐射,而避免了处理受放射性污染的生物材料的复杂性。我们研究了可变低剂量率后小鼠体内外周血白细胞DNA损伤反应的动力学137CS曝光。将C57BL / 6小鼠置于VADER中超过7天,总累积剂量高达2.7 Gy。测量外周血反应,包括白细胞耗竭,凋亡及其信号蛋白p53和DNA修复生物标志物γ-H2AX。结果表明,到第7天血白细胞数量明显下降。P53水平在第2天达到峰值(总剂量= 0.91 Gy),然后下降;γ-H2AX荧光强度(MFI)和病灶数通常随累积剂量而增加,并在第5天达到峰值(总剂量= 2.08 Gy)。γ-H2AX的ROC曲线分析可以很好地区分累积剂量<2 Gy和≥2 Gy,突出了γ-H2AXMFI在长期的环境暴露环境中作为剂量学生物标志物的潜力。

更新日期:2020-04-23
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