a Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington DC;
Radiat Res. 2014 Jan;181(1):54-64. doi: 10.1667/RR13479.1. Epub 2013 Dec 30.
Cesium-137 is a fission product of uranium and plutonium in nuclear reactors and is released in large quantities during nuclear explosions or detonation of an improvised device containing this isotope. This environmentally persistent radionuclide undergoes radioactive decay with the emission of beta particles as well as gamma radiation. Exposure to (137)Cs at high doses can cause acute radiation sickness and increase risk for cancer and death. The serious health risks associated with (137)Cs exposure makes it critical to understand how it affects human metabolism and whether minimally invasive and easily accessible samples such as urine and serum can be used to triage patients in case of a nuclear disaster or a radiologic event. In this study, we have focused on establishing a time-dependent metabolomic profile for urine collected from mice injected with (137)CsCl. The samples were collected from control and exposed mice on days 2, 5, 20 and 30 after injection. The samples were then analyzed by ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC/TOFMS) and processed by an array of informatics and statistical tools. A total of 1,412 features were identified in ESI(+) and ESI(-) modes from which 200 were determined to contribute significantly to the separation of metabolomic profiles of controls from those of the different treatment time points. The results of this study highlight the ease of use of the UPLC/TOFMS platform in finding urinary biomarkers for (137)Cs exposure. Pathway analysis of the statistically significant metabolites suggests perturbations in several amino acid and fatty acid metabolism pathways. The results also indicate that (137)Cs exposure causes: similar changes in the urinary excretion levels of taurine and citrate as seen with external-beam gamma radiation; causes no attenuation in the levels of hexanoylglycine and N-acetylspermidine; and has unique effects on the levels of isovalerylglycine and tiglylglycine.
铯-137 是核反应堆中铀和钚的裂变产物，在核爆炸或含有这种同位素的简易装置爆炸时会大量释放。这种环境持久性放射性核素通过放射性衰变，发射β粒子和γ辐射。高剂量接触 (137)Cs 会导致急性辐射病，并增加癌症和死亡的风险。与 (137)Cs 暴露相关的严重健康风险使得了解它如何影响人体代谢以及是否可以使用尿液和血清等微创和易于获取的样本对核灾难或放射事件中的患者进行分诊变得至关重要。在这项研究中，我们专注于建立从小鼠注射 (137)CsCl 后收集的尿液中随时间变化的代谢组学图谱。在注射后第 2、5、20 和 30 天，从对照和暴露小鼠中采集样本。然后通过超高效液相色谱-飞行时间质谱联用仪（UPLC/TOFMS）分析样品，并通过一系列信息学和统计工具进行处理。在正负离子模式下共鉴定出 1412 种特征，其中 200 种被确定为有助于区分对照和不同处理时间点代谢组学图谱的特征。这项研究的结果突出了 UPLC/TOFMS 平台在寻找 (137)Cs 暴露的尿液生物标志物方面的易用性。对有统计学意义的代谢物的途径分析表明，几种氨基酸和脂肪酸代谢途径受到干扰。结果还表明，(137)Cs 暴露会导致：与外照射γ辐射一样，牛磺酸和柠檬酸的尿液排泄水平发生相似的变化；不会降低己酰基甘氨酸和 N-乙酰精脒的水平；对异戊酰基甘氨酸和丁酰基甘氨酸的水平有独特的影响。
