Johns Hopkins Bloomberg School of Public Health, Environmental Health Sciences, Chair for Evidence-based Toxicology, Center for Alternatives to Animal Testing, 615 N. Wolfe St., Baltimore, MD, 21205, USA.
J Appl Toxicol. 2013 Dec;33(12):1365-83. doi: 10.1002/jat.2874. Epub 2013 May 30.
Metabolomics use in toxicology is rapidly increasing, particularly owing to advances in mass spectroscopy, which is widely used in the life sciences for phenotyping disease states. Toxicology has the advantage of having the disease agent, the toxicant, available for experimental induction of metabolomics changes monitored over time and dose. This review summarizes the different technologies employed and gives examples of their use in various areas of toxicology. A prominent use of metabolomics is the identification of signatures of toxicity - patterns of metabolite changes predictive of a hazard manifestation. Increasingly, such signatures indicative of a certain hazard manifestation are identified, suggesting that certain modes of action result in specific derangements of the metabolism. This might enable the deduction of underlying pathways of toxicity, which, in their entirety, form the Human Toxome, a key concept for implementing the vision of Toxicity Testing for the 21st century. This review summarizes the current state of metabolomics technologies and principles, their uses in toxicology and gives a thorough overview on metabolomics bioinformatics, pathway identification and quality assurance. In addition, this review lays out the prospects for further metabolomics application also in a regulatory context.
代谢组学在毒理学中的应用正在迅速增加，特别是由于质谱技术的进步，该技术在生命科学中广泛用于表型疾病状态。毒理学的优势在于有疾病因子，即毒物，可用于实验诱导代谢组学变化，同时监测时间和剂量。这篇综述总结了所采用的不同技术，并举例说明了它们在毒理学各个领域的应用。代谢组学的一个突出用途是识别毒性特征——预测危害表现的代谢物变化模式。越来越多的这样的特征被确定为特定危害表现的指示，这表明某些作用模式会导致代谢的特定紊乱。这可能使我们能够推断出毒性的潜在途径，这些途径构成了人类毒物组（Human Toxome），这是实施 21 世纪毒性测试愿景的关键概念。这篇综述总结了代谢组学技术和原理的现状，它们在毒理学中的应用，并对代谢组学生物信息学、途径识别和质量保证进行了全面概述。此外，这篇综述还阐述了在监管背景下进一步应用代谢组学的前景。
