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首页> 外文期刊>RSC Advances >Targeted metabolomics of nonhuman primate serum after exposure to ionizing radiation: potential tools for high-throughput biodosimetry
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Targeted metabolomics of nonhuman primate serum after exposure to ionizing radiation: potential tools for high-throughput biodosimetry

机译：暴露在电离辐射后的非人族灵长类动物血清的靶向性代谢组：高通量生物渗透压的潜在工具

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There is a need for research to rapidly determine an individual's absorbed dose and its potential health effects after a potential radiological or nuclear event that could expose large portions of a population to ionizing radiation (IR). Studies on biomarker identification after radiation exposure could aid in biodosimetry, identifying individual dose absorbed, as well as biologic response, and administering immediate and proper medical care. Metabolomics on easily accessible biofluids is an emerging field with potential for high-throughput biodosimetry. While tremendous effort has been put into obtaining discovery based global radiation signatures from a number of biofluids and model organisms, quantitative targeted analysis on a subset of known radiation biomarkers is required to develop an optimized panel of biomarkers for future clinical applications. The current study analyzes levels of several known broad chemical groups (acylcarnitines, amino acids, phosphatidylcholines, and biogenic amines) affected by IR in serum from nonhuman primates (NHP) 7 days after exposure through multiple reaction monitoring (MRM) analysis with a tandem quadrupole mass spectrometry (MS) platform. We identified several novel metabolites affected by IR exposure through univariate and unsupervised multivariate analyses. Levels of acylcarnitines, amino acids, and phospholipids were perturbed indicating altered protein metabolism, fatty acid β-oxidation, and inflammation. Fold changes in carnitine and short-chain acylcarnitines (acetylcarnitine, propionylcarnitine, butyrylcarnitine, and valerylcarnitine) complement previous global radiation signatures on NHP; notably, the levels of change were lower than previously observed in urine. Decreased levels of glutamate, citrulline, and arginine after IR are biomarkers indicating gastrointestinal syndrome and perturbations to the urea cycle. Sex differences were also assessed and were more prevalent in circulating acylcarnitines and phospholipids after IR exposure. These biomarkers may be combined with previously described compounds from DNA damage to develop a defined metabolomic biodosimetry panel to be analyzed by MS platforms, which are increasingly available in clinical laboratories.
机译：在潜在的放射或核事件之后，需要研究以快速确定个体的吸收剂量及其潜在的健康效果，这些放射学或核事件可能会使大部分群体暴露于电离辐射（IR）。辐射暴露后生物标志物鉴定的研究可以有助于生物渗透细量，鉴定被吸收的个体剂量，以及生物反应，并立即给药和适当的医疗保健。易于接近的Biofluids的代谢组学是一种具有高通量生物渗透压的新兴领域。虽然已经从许多生物流体和模型生物中获得了基于生物流体和模型生物的基于发现的全局辐射签名的巨大努力，但需要对未来临床应用的优化生物标志物进行定量靶向分析。目前的研究分析了通过多次反应监测（MRM）分析与串联四极其在暴露后7天受到IR在血清中受到IR的几种已知宽化学基团（酰基氨基甲酰胺，氨基酸，磷脂酰胆碱和生物胺）的水平。质谱（MS）平台。我们通过单变量和无调节多变量分析确定了由IR暴露影响的几种新代谢物。酰基甘油氨酸，氨基酸和磷脂的水平扰动表明改变的蛋白质代谢，脂肪酸β-氧化和炎症。尿素和短链酰基氨基碱（乙酰氨基，丙氨酸，丙氨酸，丁酰基氨基，和valerylcarnitine）在NHP中补充以前的全球辐射签名的折叠变化;值得注意的是，变化水平低于尿液中以前观察到的水平。 IR后谷氨酸，瓜氨酸和精氨酸水平降低，所述生物标志物指示胃肠综合征和尿素循环的扰动。还评估了性差异，并且在红外线暴露后循环酰基羧碱和磷脂中更普遍。这些生物标志物可以与先前描述的来自DNA损伤的化合物组合，以通过MS平台进行分析的确定的代谢物生物渗透蛋白基板，这在临床实验室中越来越多地提供。

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