Comparative metabolic profiles of total and partial body radiation exposure in mice using an untargeted metabolomics approach
Comparative metabolic profiles of total and partial body radiation exposure in mice using an untargeted metabolomics approach
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DOI：
10.1007/s11306-020-01742-7
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发表时间：
2020-12-01
期刊：
影响因子：
3.6
通讯作者：
Rana, Poonam
中科院分区：
文献类型：
--
作者：
Maan, Kiran;Tyagi, Ritu;Rana, Poonam
在有意或无意的核事故中，大量人群暴露于电离辐射，无疑会产生一个复杂的情景，包括全身和局部受辐射的受害者。迫切需要一种基于高通量技术的快速评估方法来对暴露对象进行分层，而不依赖于暴露是均匀的全身还是非均匀的局部身体。目的采用核磁共振（NMR）代谢组学方法，比较和鉴定全辐射和部分辐射小鼠模型中候选代谢物的差异表达。方法C57BL/6雄性小鼠（8 ~ 10周龄）以10 Gy γ射线照射全身或胸、后肢、腹部局部。使用高分辨率核磁共振波谱检查照射后24小时收集的尿液样本，并使用多变量分析对数据集进行分析。结果对辐射后24 h收集的尿液样本进行多变量分析和代谢途径分析显示，所有辐照组与对照组存在分离。与能量代谢、肠道菌群代谢和牛磺酸相关的代谢物在局部和全身照射中都是常见的，因此它们是辐射暴露的潜在候选者。然而，在部分身体暴露组中观察到明显的代谢模式，后肢区域观察到的变化最大，表明不同的组织相关辐射敏感性。器官特异性变化可能为辐射损伤后处于危险中的生理系统提供早期预警。结论本研究肯定了代谢物标记物的潜力，对比分析可为综合解决辐射生物标记物的复杂研究问题提供重要信息。
Introduction A large scale population exposure to ionizing radiation during intentional or unintentional nuclear accidents undoubtedly generates a complex scenario with partial-body as well as total-body irradiated victims. A high throughput technique based rapid assessment method is an urgent necessity for stratification of exposed subjects independent of whether exposure is uniform total-body or non-homogenous partial-body. Objective Here, we used Nuclear Magnetic Resonance (NMR) based metabolomics approach to compare and identify candidate metabolites differentially expressed in total and partially irradiated mice model. Methods C57BL/6 male mice (8-10 weeks) were irradiated total-body or locally to thoracic, hind limb or abdominal regions with 10 Gy of gamma radiation. Urine samples collected at 24 h post irradiation were examined using high resolution NMR spectroscopy and the datasets were analysed using multivariate analysis. Results Multivariate and metabolic pathway analysis in urine samples collected at 24 h post-radiation exhibited segregation of all irradiated groups from controls. Metabolites associated with energy metabolism, gut flora metabolism and taurine were common to partial and total-body irradiation, thus making them potential candidates for radiation exposure. Nevertheless, a distinct metabolic pattern was observed in partial-body exposed groups with maximum changes observed in the hind limb region indicating differential tissue associated radiation sensitivity. The organ-specific changes may provide an early warning regarding the physiological system at risk after radiation injury. Conclusion The study affirms potentiality of metabolite markers and comparative analysis could be an important piece of information for an integrated solution to a complex research question in terms of radiation biomarkers.