NMR-based metabonomics in toxicology research

Abstract

The search for biomarkers of toxicity and disease is one of the major research initiatives at the National Center for Toxicological Research (NCTR) of the FDA. A systems biology approach that integrates biomarkers from functional genomics, proteomics and metabonomics research into a comprehensive understanding of toxicological events and disease states has been initiated at the NCTR. Since genomics, proteomics and metabonomics have become accepted research platforms within the pharmaceutical industry, understanding 'omics' research has become a priority for the FDA. Thus, 'omics' research falls within the NCTR mission statement on the NCTR public website that is defined as "to conduct peer-reviewed scientific research that supports and anticipates the FDA's current and future regulatory needs. This involves fundamental and applied research specifically designed to define biological mechanisms of action underlying the toxicity of products regulated by the FDA." The goals of our metabonomics research are to investigate and validate metabonomics drug toxicity results (Robertson et al., 2000) and to use systems biology approaches to understand toxic mechanisms and disease states (Aardema and MacGregor, 2002; Nicholson and Wilson, 2003; Coen et al., 2004). Transcriptomics describes the analysis of gene expression while proteomics is the comprehensive analysis of the proteome. Metabonomics evaluates the temporal changes in cell metabolism, which is downstream from genomic and proteomic events. Monitoring the changes in the cellular concentrations of metabolites represents an opportunity to identify phenotypical responses to drug toxicity and disease state (Fiehn, 2002). © 2005 Springer Science+Business Media, Inc. All rights reserved.