Radiation metabolomics. 3. Biomarker discovery in the urine of gamma-irradiated rats using a simplified metabolomics protocol of gas chromatography-mass spectrometry combined with random forests machine learning algorithm.
Radiation metabolomics. 3. Biomarker discovery in the urine of gamma-irradiated rats using a simplified metabolomics protocol of gas chromatography-mass spectrometry combined with random forests machine learning algorithm.
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DOI：
10.1667/rr1796.1
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发表时间：
2009-08
影响因子：
3.4
通讯作者：
Idle JR
中科院分区：
文献类型：
--
作者：
Lanz C;Patterson AD;Slavík J;Krausz KW;Ledermann M;Gonzalez FJ;Idle JR
使用质谱学技术的辐射代谢组学代表了高通量微创辐射生物剂量学的一种可能的手段。描述了一种简化的代谢组学方法，该方法利用无处不在的气相色谱-质谱仪和包括随机森林机器学习算法在内的开源软件，在大鼠体内发现3GYγ辐射的潜在生物标志物。Wistar雄性大鼠6只，假照射对照组6只，照射前4只，照射后3只，连续7天。水和食物的消耗、尿量、体重以及钠、钾、钙、氯、磷和尿素的排泄都受到γ辐射的主要影响。代谢组学方案发现，由于辐射暴露，几种尿代谢物显著上调(乙醛、苏氨酸、胸腺嘧啶、尿嘧啶、对甲酚)和下调(柠檬酸、2-氧戊二酸、己二酸、戊二酸、琥珀酸、杜鹃酸)。胸腺嘧啶和尿嘧啶被证明主要来自胸腺嘧啶核苷和2‘-脱氧尿嘧啶核苷，这是小鼠已知的辐射生物标志物。大鼠的辐射代谢表型似乎源于氧化应激和对肾功能的影响。气相色谱-质谱法是进一步发展辐射代谢组学领域和辅助设计用于检测环境辐射生物后果的仪器的一个很有前途的平台。
Radiation metabolomics employing mass spectral technologies represents a plausible means of high-throughput minimally invasive radiation biodosimetry. A simplified metabolomics protocol is described that employs ubiquitous gas chromatography-mass spectrometry and open source software including random forests machine learning algorithm to uncover latent biomarkers of 3 Gy γ radiation in rats. Urine was collected from six male Wistar rats and six sham-irradiated controls for 7 days, 4 prior to irradiation and 3 after irradiation. Water and food consumption, urine volume, body weight, and sodium, potassium, calcium, chloride, phosphate and urea excretion showed major effects from exposure to γ radiation. The metabolomics protocol uncovered several urinary metabolites that were significantly up-regulated (glyoxylate, threonate, thymine, uracil, p-cresol) and down-regulated (citrate, 2-oxoglutarate, adipate, pimelate, suberate, azelaate) as a result of radiation exposure. Thymine and uracil were shown to derive largely from thymidine and 2′-deoxyuridine, which are known radiation biomarkers in the mouse. The radiation metabolomic phenotype in rats appeared to derive from oxidative stress and effects on kidney function. Gas chromatography-mass spectrometry is a promising platform on which to develop the field of radiation metabolomics further and to assist in the design of instrumentation for use in detecting biological consequences of environmental radiation release.