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Effect of dose and dose rate on temporal γ-H2AX kinetics in mouse blood and spleen mononuclear cells in vivo following Cesium-137 administration
BMC Molecular and Cell Biology ( IF 2.8 ) Pub Date : 2019-05-28 , DOI: 10.1186/s12860-019-0195-2
Helen C. Turner , Younghyun Lee , Waylon Weber , Dunstana Melo , Aimee Kowell , Shanaz A. Ghandhi , Sally A. Amundson , David J. Brenner , Igor Shuryak

Cesium-137 (137Cs) is one of the major and most clinically relevant radionuclides of concern in a radiological dispersal device, “dirty bomb” scenario as well as in nuclear accidents and detonations. In this exposure scenario, a significant amount of soluble radionuclide(s) may be dispersed into the atmosphere as a component of fallout. The objectives of the present study were to investigate the effect of protracted 137Cs radionuclide exposures on DNA damage in mouse blood and spleen mononuclear cells (MNCs) in vivo using the γ-H2AX biomarker, and to develop a mathematical formalism for these processes. C57BL/6 mice were injected with a range of 137CsCl activities (5.74, 6.66, 7.65 and 9.28 MBq) to achieve total-body committed doses of ~ 4 Gy at Days 3, 5, 7, and 14. Close to 50% of 137Cs was excreted by day 5, leading to a slower rate of decay for the remaining time of the study; 137Cs excretion kinetics were independent of activity level within the tested range, and the absorbed radiation dose was determined by injected activity and time after injection. Measurements of γ-H2AX fluorescence in blood and spleen MNCs at each time point were used to develop a new biodosimetric mathematical formalism to estimate injected activity based on γ-H2AX fluorescence and time after injection. The formalism performed reasonably well on blood data at 2–5 days after injection: Pearson and Spearman’s correlation coefficients between actual and predicted activity values were 0.857 (p = 0.00659) and 0.929 (p = 0.00223), respectively. Despite the complicated nature of the studied biological system and the time-dependent changes in radiation dose and dose rate due to radionuclide excretion and other processes, we have used the γ-H2AX repair kinetics to develop a mathematical formalism, which can relatively accurately predict injected 137Cs activity 2–5 days after initial exposure. To determine the assay’s usefulness to predict retrospective absorbed dose for medical triage, further studies are required to validate the sensitivity and accuracy of the γ-H2AX response after protracted exposures.

中文翻译:

施用铯137后剂量和剂量率对小鼠血液和脾单核细胞中时间γ-H2AX动力学的影响

铯137(137Cs)是放射性扩散装置,“脏弹”场景以及核事故和爆炸中关注的主要和临床上最相关的放射性核素之一。在这种暴露情况下,大量的可溶性放射性核素可能会作为沉降物的一部分散布到大气中。本研究的目的是使用γ-H2AX生物标记物研究137Cs放射性核素长时间暴露对小鼠血液和脾单核细胞(MNC)中DNA损伤的影响,并为这些过程建立数学形式。C57BL / 6小鼠被注射一系列137CsCl活性(5.74、6.66、7.65和9.28 MBq),以在第3、5、7和14天达到约4 Gy的全身定剂量。接近137Cs的50%在第5天被排泄 导致研究剩余时间的衰减率降低;137 Cs的排泄动力学与测试范围内的活性水平无关,吸收的辐射剂量由注入的活性和注入后的时间确定。在每个时间点测量血液和脾MNC中的γ-H2AX荧光,以开发一种新的生物剂量学数学形式,以基于γ-H2AX荧光和注射后的时间估算注射活性。注射后2-5天,血液数据的形式主义表现相当好:实际和预期活性值之间的Pearson和Spearman相关系数分别为0.857(p = 0.00659)和0.929(p = 0.00223)。尽管所研究的生物系统性质复杂,并且由于放射性核素排泄和其他过程而导致辐射剂量和剂量率随时间变化,但我们仍使用γ-H2AX修复动力学来建立数学形式,可以相对准确地预测注射剂量。初次接触后2-5天,137Cs的活性。为了确定该测定法用于预测医学分类的回顾性吸收剂量的有效性,需要进一步的研究以验证长时间暴露后γ-H2AX反应的敏感性和准确性。
更新日期:2019-05-28
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