ABSTRACT
In the discipline of pharmacology, the “ome” revolution (the genome, transcriptome, proteome,
and metabolome) has merged to create the toxicogenome and the pharmacogenome.
The evolution of these disciplines has been made possible by the convergence of rapidly
developing technological advances for the detection of gene expression levels and the
identification of proteins and small molecules on automated platform arrays. These arrays
are able to simultaneously evaluate the individual components of complex samples, whose
identity is predicted by sophisticated bioinformatics software requiring powerful compu-
tational analysis. These technological advances in combination with the completion of the
genomes of humans, and the traditional animals used in preclinical drug toxicity studies, mice
and rats, are predicted to rapidly lead to major advances for both the diagnosis of drug-induced
liver disease and for an enhanced understanding of their molecular mechanisms of toxicity.
Future technological advances such as global analysis of lipids, carbohydrates, and lipoproteins
will no doubt contribute to these fields. Drug mechanisms coupled with variations in host
response due to genomic polymorphisms and environmental factors, such as coadministrations
of drugs or concurrent conditions, will define how host factors may render individuals more
susceptible to drug-induced liver disease. Besides providing new biomarkers, changes in gene
expression profile hint at specific pathways, which gives clues to the mechanism of drug
hepatotoxicity, opening new areas for investigation of both the mechanism and prevention of
liver injury. In this chapter, the methodology of the transcriptomic, genomic, proteomic, and
metabolomics profiling will be reviewed with pertinent examples that specifically relate to
hepatotoxicity. The role of gene polymorphisms in drug metabolic enzymes will be reviewed
followed by a summary of the anticipated future advances in the field and how this will impact
the evaluation of drug-induced liver disease. Several excellent reviews are suggested for a more
global overview of this exciting and rapidly evolving field of pharmacology (1-3).
