Radiation metabolomics. 4. UPLC-ESI-QTOFMS-Based metabolomics for urinary biomarker discovery in gamma-irradiated rats.
Radiation metabolomics. 4. UPLC-ESI-QTOFMS-Based metabolomics for urinary biomarker discovery in gamma-irradiated rats.
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DOI：
10.1667/rr2437.1
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发表时间：
2011-04
影响因子：
3.4
通讯作者：
Idle JR
中科院分区：
文献类型：
--
作者：
Johnson CH;Patterson AD;Krausz KW;Lanz C;Kang DW;Luecke H;Gonzalez FJ;Idle JR
辐射代谢组学有助于通过超高效液相色谱-飞行时间质谱（UPLC-ESI-QTOFMS）鉴定细胞和小鼠中的许多生物标志物，并通过气相色谱-质谱（GCMS）鉴定大鼠中的生物标志物。这些标志物已被证明是剂量和时间依赖性的。在此，使用UPLC-ESI-QTOFMS分析7天内从12只大鼠采集的大鼠尿液样品;在代谢笼适应4天后，对它们进行假照射或3戈伊γ照射。利用多元数据分析，确定了9种大鼠γ辐射尿生物标志物，包括一种新的哺乳动物代谢物N-乙酰牛磺酸。这些上调的尿生物标志物通过串联质谱法和与真实标准的比较来证实。它们包括胸苷、2 ′-脱氧尿苷、2 ′-脱氧黄苷、N1-乙酰亚精胺、N-乙酰氨基葡萄糖/半乳糖胺-6-硫酸盐、N-乙酰牛磺酸、N-己酰甘氨酸、牛磺酸和羟乙基磺酸。在这些代谢物中，先前通过GCMS（观察为尿苷和胸腺嘧啶）在大鼠中以及通过UPLC-ESI-QTOFMS在小鼠中鉴别了2 ′-脱氧尿苷和胸苷。UPLC-ESI-QTOFMS还检测到2 ′脱氧黄嘌呤核苷、牛磺酸和N-己酰甘氨酸。这些现在是明确的跨物种生物标志物电离辐射照射。下调的生物标志物显示与食物剥夺和饥饿机制有关。UPLC-ESI-QTOFMS方法有助于发现电离辐射暴露的常见生物标志物。
Radiation metabolomics has aided in the identification of a number of biomarkers in cells and mice by ultra-performance liquid chromatography-coupled time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and in rats by gas chromatography-coupled mass spectrometry (GCMS). These markers have been shown to be both dose- and time-dependent. Here UPLC-ESI-QTOFMS was used to analyze rat urine samples taken from 12 rats over 7 days; they were either sham-irradiated or γ-irradiated with 3 Gy after 4 days of metabolic cage acclimatization. Using multivariate data analysis, nine urinary biomarkers of γ radiation in rats were identified, including a novel mammalian metabolite, N-acetyltaurine. These upregulated urinary biomarkers were confirmed through tandem mass spectrometry and comparisons with authentic standards. They include thymidine, 2′-deoxyuridine, 2′deoxyxanthosine, N1-acetylspermidine, N-acetylglucosamine/galactosamine-6-sulfate, N-acetyltaurine, N-hexanoylglycine, taurine and, tentatively, isethionic acid. Of these metabolites, 2′-deoxyuridine and thymidine were previously identified in the rat by GCMS (observed as uridine and thymine) and in the mouse by UPLC-ESI-QTOFMS. 2′Deoxyxanthosine, taurine and N-hexanoylglycine were also seen in the mouse by UPLC-ESI-QTOFMS. These are now unequivocal cross-species biomarkers for ionizing radiation exposure. Downregulated biomarkers were shown to be related to food deprivation and starvation mechanisms. The UPLC-ESI-QTOFMS approach has aided in the advance for finding common biomarkers of ionizing radiation exposure.