Journal
TOXICOLOGY LETTERS
Volume 149, Issue 1-3, Pages 371-375Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2003.12.045
Keywords
toxicogenomics; predictive toxicology; mechanism-based risk assessment; review
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Genomics has had an impact on two areas of drug development, predictive toxicology and mechanism-based risk assessment. Predictive toxicology studies are aimed at identifying the potential for a compound to be toxic. By developing databases of expression profiles for a wide variety of toxic compounds and toxic models it has been possible to create statistical and computational methods which provide an indication of the toxic potential of a drug from the pattern of gene expression changes it elicits in in vitro or in vivo systems. Because gene expression is central to many responses to xenobiotics, genomic approaches lend themselves very readily to mechanistic toxicology studies. By examining changes in gene expression in cells and tissues in response to drugs it is possible to generate hypotheses as to the underlying mechanism and in some cases it is possible to evaluate hypotheses of toxic mechanism. Some concerns remain about the use of the technology but toxicogenomics can no longer be regarded as new technology in drug development. The investments made in applying the technology are maturing and there is a determined effort to bring the full power of the technology into drug development. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
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