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Metabolic profiling in Caenorhabditis elegans provides an unbiased approach to investigations of dosage dependent lead toxicity

机译:秀丽隐杆线虫的代谢谱分析为研究剂量依赖性铅毒性提供了一种公正的方法

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摘要

The nematode, Caenorhabditis elegans (CE), serves as a model system in which to explore the impact of particularly low-levels of lead [250, 500, 1000 and 2000 parts per million (ppm) (1.4×10−6 M to 1.1×10−5 Mematode)] on specific metabolic pathways and processes. Chromatographic profiles of redox active metabolites are captured through application of high performance liquid chromatography coupled to electrochemical detection (Coularray/HPLC). Principal Component Analysis (PCA: unbiased cluster analysis) and the application of a slicing program, located significant areas of difference occurring within the 2.8–4.58min section of the chromatograms. It is within this region of the data profiles that known components of the purine pathway reside. Two analytes of unknown structure were detected at 3.5 and 4min respectively. Alterations in levels of the purine, tryptophan and tyrosine pathway intermediates measured in response to differing concentrations of lead acetate indicate that the effect of lead on these pathways is not linear, yet the ratio of the pathway precursors, tryptophan and tyrosine remains relatively constant. The application of the above combined analytical approaches enhances the value of data generated. Exposure of CE to very low levels of lead produced significant alterations in profiles of electrochemically active compounds.
机译:线虫秀丽隐杆线虫(CE)是一个模型系统,可用于研究极低水平的铅[250、500、1000和2000百万分之(ppm)(1.4×10-6 M至1.1 ×10-5 M /线虫)]上特定的代谢途径和过程。氧化还原活性代谢物的色谱图可通过应用高效液相色谱和电化学检测(Coularray / HPLC)来捕获。主成分分析(PCA:无偏聚类分析)和切片程序的应用,在色谱图的2.8–4.58min区域内发现了明显的差异区域。嘌呤途径的已知成分位于数据概况的该区域内。分别在3.5和4min处检测到两种结构未知的分析物。响应于不同浓度的乙酸铅而测得的嘌呤,色氨酸和酪氨酸途径中间体水平的变化表明,铅对这些途径的影响不是线性的,但是途径前体,色氨酸和酪氨酸的比例保持相对恒定。上述组合分析方法的应用提高了所生成数据的价值。 CE暴露于非常低的铅含量会导致电化学活性化合物的轮廓发生重大变化。

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