The Application of Toxicogenomics to the Interpretation of Toxicologic Pathology

Abstract Techniques that measure hundreds to thousands of molecules in samples of tissues, urine, or blood (e.g., DNA microarrays, high-throughput DNA sequencing, endogenous metabolite profiling with mass spectroscopy or nuclear magnetic resonance) have become increasingly accessible to the toxicologic pathologist. Application of these methods to understand and characterize xenobiotic-induced pathology is termed toxicogenomics . This new field also encompasses the molecular characterization of normal and disease-associated pathologies since judgments of adverse and drug-related effects rely on these referents. Focusing on transcriptomics (large-scale assays of messenger RNAs) and metabolomics (large-scale assays of endogenous metabolites), this chapter explores the key strengths and weaknesses of toxicogenomics as applied to toxicologic pathology and describes the key issues and methods employed in toxicogenomic study conduct. The chapter illustrates how the toxicologic pathologist can effectively participate in as well as guide and instruct toxicogenomic practices; provides specific examples of momentous toxicogenomic studies; and predicts future directions of toxicogenomics over the next decades.