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Toxicogenomics and the Evolution of Systems Toxicology

Molecular and Cellular Aspects of Toxicology

  1. Michael D. Waters PhD1,
  2. B. Alex Merrick PhD2

Published Online: 15 DEC 2009

DOI: 10.1002/9780470744307.gat026

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

Waters, M. D. and Alex Merrick, B. 2009. Toxicogenomics and the Evolution of Systems Toxicology. General, Applied and Systems Toxicology. .

Author Information

  1. 1

    Integrated Laboratory Systems (ILS), Chief Scientific Officer, Research Triangle Park, North Carolina, USA

  2. 2

    National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

Publication History

  1. Published Online: 15 DEC 2009

Abstract

Toxicogenomics combines toxicology with genetics and genomics to provide a comprehensive view of the function of the genetic and biochemical machinery (genes, proteins and metabolites) of the living cell. A critical part of the study of toxicology, and by extension, toxicogenomics, is the empirical and contextual characterization of adverse effects at the various levels of organization of the organism—ranging from animal health and function to organs, tissues, cells and intracellular and intercellular molecular systems. Thus, toxicology and toxicogenomics are rapidly evolving into systems toxicology. The modern achievements of sequencing whole genomes have been quickly followed by gene expression profiling technologies that allow comprehensive queries of the transcriptome, to the refinement of traditional proteomics, and to the creation of other -omic technologies. Toxicogenomics evolved from the desire to characterize how genomes respond to environmental stressors or toxicants by combining genome-wide mRNA expression profiling (transcriptomics) with global protein expression patterns (proteomics) that are interpreted by the use of bioinformatics to understand the role of gene–environment interactions in disease and dysfunction. The inherently reductive nature of toxicogenomic analysis down to the level of DNA, mRNA and protein sequences is being counterbalanced by a concerted attempt to reassemble these molecular pieces of information into pathways and networks that form the new field of systems toxicology. The result of these concurrent reductive and assembly activities in gene expression information is a much greater depth of field now possible for examining toxicant responses. The ability to discern mechanisms of toxicity as related to health issues is an important challenge facing scientists, public health decision-makers and regulatory authorities, whose aim is to protect humans and the environment from exposures to hazardous drugs, chemicals and environmental stressors. The problems of performing safety and risk assessments for drugs and chemicals and of identifying environmental factors involved in the aetiology of human disease have long been formidable issues. Genomic technologies offer the potential to change the way in which toxicity and human health risk are assessed. This review explores the new field of toxicogenomics, delineates some of its research approaches and success stories and describes the challenges it faces as it enters the new world of systems toxicology.

Keywords:

  • toxicogenomics;
  • transcriptomics;
  • proteomics;
  • metabolomics;
  • metabonomics;
  • toxicoproteomics;
  • systems toxicology