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代谢组学在辐射生物剂量测定中的应用:通过小分子探索辐射效应。

Metabolomic applications in radiation biodosimetry: exploring radiation effects through small molecules.

作者信息

Pannkuk Evan L, Fornace Albert J, Laiakis Evagelia C

机构信息

a Tumor Biology Program , Lombardi Comprehensive Cancer Center, Georgetown University , Washington DC , USA.

b Molecular Oncology , Lombardi Comprehensive Cancer Center, Georgetown University , Washington DC , USA.

出版信息

Int J Radiat Biol. 2017 Oct;93(10):1151-1176. doi: 10.1080/09553002.2016.1269218. Epub 2017 Jan 12.

Abstract

PURPOSE

Exposure of the general population to ionizing radiation has increased in the past decades, primarily due to long distance travel and medical procedures. On the other hand, accidental exposures, nuclear accidents, and elevated threats of terrorism with the potential detonation of a radiological dispersal device or improvised nuclear device in a major city, all have led to increased needs for rapid biodosimetry and assessment of exposure to different radiation qualities and scenarios. Metabolomics, the qualitative and quantitative assessment of small molecules in a given biological specimen, has emerged as a promising technology to allow for rapid determination of an individual's exposure level and metabolic phenotype. Advancements in mass spectrometry techniques have led to untargeted (discovery phase, global assessment) and targeted (quantitative phase) methods not only to identify biomarkers of radiation exposure, but also to assess general perturbations of metabolism with potential long-term consequences, such as cancer, cardiovascular, and pulmonary disease.

CONCLUSIONS

Metabolomics of radiation exposure has provided a highly informative snapshot of metabolic dysregulation. Biomarkers in easily accessible biofluids and biospecimens (urine, blood, saliva, sebum, fecal material) from mouse, rat, and minipig models, to non-human primates and humans have provided the basis for determination of a radiation signature to assess the need for medical intervention. Here we provide a comprehensive description of the current status of radiation metabolomic studies for the purpose of rapid high-throughput radiation biodosimetry in easily accessible biofluids and discuss future directions of radiation metabolomics research.

摘要

目的

在过去几十年中,普通人群受到的电离辐射暴露有所增加,主要原因是长途旅行和医疗程序。另一方面,意外暴露、核事故以及恐怖主义威胁升级,可能在大城市引爆放射性散布装置或简易核装置,所有这些都导致对快速生物剂量测定以及评估不同辐射质量和场景下的暴露情况的需求增加。代谢组学是对给定生物样本中的小分子进行定性和定量评估,已成为一种有前景的技术,可用于快速确定个体的暴露水平和代谢表型。质谱技术的进步催生了非靶向(发现阶段,全局评估)和靶向(定量阶段)方法,不仅用于识别辐射暴露的生物标志物,还用于评估代谢的一般扰动及其可能产生的长期后果,如癌症、心血管疾病和肺部疾病。

结论

辐射暴露的代谢组学提供了代谢失调的高度信息丰富的概况。从小鼠、大鼠和小型猪模型到非人灵长类动物和人类,易于获取的生物流体和生物样本(尿液、血液、唾液、皮脂、粪便物质)中的生物标志物为确定辐射特征以评估医疗干预需求提供了基础。在此,我们全面描述了辐射代谢组学研究的现状,目的是在易于获取的生物流体中进行快速高通量辐射生物剂量测定,并讨论辐射代谢组学研究的未来方向。

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