The goal of this proposal is to develop and validate a process for generating in vitro, gene expression assays for toxicology. Specifically, we propose to derive gene signatures, that can classify chemicals according to specific liver pathology endpoints, using whole genome expression profiling in rat primary hepatocytes in vitro and to convert the gene signatures into efficient, high throughput, validated assays for use as a cost efficient, fast screening tool. The project will utilize the joint expertise of Iconix researchers in identifying toxicological gene signatures using compound treatment and global, microarray gene expression analysis, and Althea researchers for translating these signatures into high throughput gene expression assays using highly multiplexed, universal-primed rtPCR (UP-rtPCR). In this Phase I proposal, we intend to demonstrate the process for one general hepatoxicity endpoint, Cholestatis, and one general toxicity endpoint, DNA damage
