Use of Traditional End Points and Gene Dysregulation to Understand Mechanisms of Toxicity: Toxicogenomics in Mechanistic Toxicology

Abstract

Microarray technologies can be used to generate massive amounts of gene expression information as an initial step to decipher the molecular mechanisms of toxicologic changes. Identifying genes whose expression is associated with specific toxic end points is an initial step in predicting, characterizing, and understanding toxicity. Analysis of gene function and the chronology of gene expression changes represent additional methods to generate hypotheses of the mechanisms of toxicity. Follow-up experiments are typically required to confirm or refute hypotheses derived from toxicogenomic data. Understanding the mechanism of toxicity for a compound is a critical step in forming a rational plan for developing counterscreens for toxicity and for increasing productivity of research and development while decreasing the risk of late-stage failure in pharmaceutical development.