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Toxicogenomics concepts and applications to study hepatic effects of food additives and chemicals

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Author: Stierum, R. · Heijne, W. · Kienhuis, A. · Ommen, B. van · Groten, J.
Type:article
Date:2005
Institution: TNO Kwaliteit van Leven
Source:Toxicology and Applied Pharmacology, 2 SUPPL., 207
Identifier: 238674
doi: doi:10.1016/j.taap.2005.01.050
Keywords: Toxicology Nutrition · Physiological Sciences · In vitro · In vivo · Liver · Toxicogenomics · bromobenzene · butylcresol · chemical compound · curcumin · food additive · gallic acid propyl ester · proteome · tiabendazole · transcriptome · biochemistry · bioinformatics · comparative toxicology · conference paper · disease marker · DNA fingerprinting · gene expression profiling · genetic procedures · genetic toxicology · genomics · in vitro study · in vivo study · laboratory · liver toxicity · metabolomics · molecular biology · nonhuman · prediction · proteomics · rat · technology · toxicological parameters · transcriptomics · Animals · Food Additives · Genomics · Humans · Liver · Toxicology

Abstract

Transcriptomics, proteomics and metabolomics are genomics technologies with great potential in toxicological sciences. Toxicogenomics involves the integration of conventional toxicological examinations with gene, protein or metabolite expression profiles. An overview together with selected examples of the possibilities of genomics in toxicology is given. The expectations raised by toxicogenomics are earlier and more sensitive detection of toxicity. Furthermore, toxicogenomics will provide a better understanding of the mechanism of toxicity and may facilitate the prediction of toxicity of unknown compounds. Mechanism-based markers of toxicity can be discovered and improved interspecies and in vitro-in vivo extrapolations will drive model developments in toxicology. Toxicological assessment of chemical mixtures will benefit from the new molecular biological tools. In our laboratory, toxicogenomics is predominantly applied for elucidation of mechanisms of action and discovery of novel pathway-supported mechanism-based markers of liver toxicity. In addition, we aim to integrate transcriptome, proteome and metabolome data, supported by bioinformatics to develop a systems biology approach for toxicology. Transcriptomics and proteomics studies on bromobenzene-mediated hepatotoxicity in the rat are discussed. Finally, an example is shown in which gene expression profiling together with conventional biochemistry led to the discovery of novel markers for the hepatic effects of the food additives butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole. © 2005 Elsevier Inc. All rights reserved.