Data from: Potential New Method of Mixture Effects Testing Using Metabolomics and Caenorhabditis elegans

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The development of superior tools for molecular and computational biology in recent years has provided an opportunity for the creation of faster toxicological screens that are relevant for, but do not rely on, mammalian systems. In this study, NMR spectroscopy and GC-MS based metabolomics have been used in conjunction with multivariate statistics to examine the metabolic changes in the nematode Caenorhabditis elegans following exposure to different concentrations of the heavy metal nickel, the pesticide chlorpyrifos, and their mixture. Novel metabolic profiles were associated with both exposure and dose level. The biochemical responses were more closely matched when exposure was at the same effect level, even for different chemicals, than when exposure was for different levels of the same chemical (e.g., low versus high dose). Responses to the mixture reflected the contribution of the chemicals to the overall exposure. In common with the metabolic responses of several other species exposed to the same chemicals, we observed changes in branch chain amino acids and tricarboxylic acid cycle intermediates. These results form the basis for a rapid and economically viable toxicity test that defines the molecular effects of pollution/toxicant exposure in a manner that is relevant to higher vertebrates.

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近年来，分子生物学与计算生物学领域高性能研究工具的发展，为构建无需依赖哺乳动物体系、但仍与哺乳动物体系相关的快速毒理学筛选方法提供了契机。本研究采用基于核磁共振波谱法（NMR spectroscopy）与气相色谱-质谱联用（GC-MS）的代谢组学技术，并结合多元统计分析，探究了秀丽隐杆线虫（Caenorhabditis elegans）暴露于不同浓度重金属镍、杀虫剂毒死蜱及其混合制剂后的代谢变化。新型代谢特征与暴露条件及剂量水平均存在关联。当暴露处于相同效应水平时，即便使用不同化学物质，其生化响应的匹配度也高于同一化学物质不同暴露水平（如低剂量与高剂量）时的匹配度。混合制剂的暴露响应体现了各组分化学物质对整体暴露的贡献情况。与其他多种暴露于同类化学物质的物种的代谢响应一致，本研究观察到支链氨基酸与三羧酸循环中间产物的含量变化。本研究结果为构建快速且经济可行的毒性测试方法奠定了基础，该方法能够以契合高等脊椎动物的方式阐明污染物/有毒物质暴露的分子效应。