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全鼠血 microRNA 作为 γ 射线和(56)Fe 离子暴露的生物标志物。

Whole mouse blood microRNA as biomarkers for exposure to γ-rays and (56)Fe ion.

机构信息

Center for Radiological Research, Columbia University Medical Center, New York, NY, USA.

出版信息

Int J Radiat Biol. 2011 Jul;87(7):653-62. doi: 10.3109/09553002.2010.549537. Epub 2011 Jan 28.

Abstract

PURPOSE

Biomarkers of ionising radiation exposure are useful in a variety of scenarios, such as medical diagnostic imaging, occupational exposures, and spaceflight. This study investigates to what extent microRNA (miRNA) expression signatures in mouse peripheral blood can be used as biomarkers for exposures to radiation with low and high linear energy transfers.

MATERIALS AND METHODS

Mice were irradiated with doses of 0.5, 1.5, or 5.0 Gy γ-rays (dose rate of 0.0136 Gy/s) or with doses of 0.1 or 0.5 Gy (56)Fe ions (dose rate of 0.00208 Gy/s). Total RNA was isolated from whole blood at 6 h or 24 h after irradiation. Three animals per irradiation condition were used. Differentially expressed miRNA were determined by means of quantitative real-time polymerase chain reaction.

RESULTS

miRNA expression signatures were radiation type-specific and dose- and time-dependent. The differentially expressed miRNA were expressed in either one condition (71%) or multiple conditions (29%). Classifiers based on the differentially expressed miRNA predicted radiation type or dose with accuracies between 75% and 100%. Gene-ontology analyses show that miRNA induced by irradiation are involved in the control of several biological processes, such as mRNA transcription regulation, nucleic-acid metabolism, and development.

CONCLUSION

miRNA signatures induced by ionising radiation in mouse blood are radiation type- and radiation dose-specific. These findings underline the complexity of the radiation response and the importance of miRNA in it.

摘要

目的

电离辐射暴露的生物标志物在多种情况下都很有用,例如医学诊断成像、职业暴露和航天飞行。本研究旨在探讨小鼠外周血中的 microRNA(miRNA)表达谱在多大程度上可以作为低和高线性能量转移辐射暴露的生物标志物。

材料和方法

用 0.5、1.5 或 5.0 Gy γ 射线(剂量率为 0.0136 Gy/s)或 0.1 或 0.5 Gy(56)Fe 离子(剂量率为 0.00208 Gy/s)照射小鼠。照射后 6 小时或 24 小时从全血中分离总 RNA。每个照射条件下使用 3 只动物。通过实时定量聚合酶链反应确定差异表达的 miRNA。

结果

miRNA 表达谱具有辐射类型特异性、剂量和时间依赖性。差异表达的 miRNA 要么在一种条件下表达(71%),要么在多种条件下表达(29%)。基于差异表达 miRNA 的分类器预测辐射类型或剂量的准确率在 75%至 100%之间。基因本体分析表明,受照射诱导的 miRNA 参与了多个生物学过程的调控,如 mRNA 转录调控、核酸代谢和发育。

结论

小鼠血液中电离辐射诱导的 miRNA 特征具有辐射类型和辐射剂量特异性。这些发现强调了辐射反应的复杂性以及 miRNA 在其中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3010/3586327/228a4feba3bf/nihms440583f1.jpg

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