Possible implications of in vitro assay system for toxicity evaluation using DNA microarray

Abstract

Toxicological profiles obtained from DNA microarray experiments are becoming increasingly important in toxicity evaluations. Many research groups are carrying out toxicogenomic studies to develop toxicological expression profiles of exposure to chemicals that can be applied to human and environmental monitoring. Although a wide range of in vivo and in vitro systems are used to obtain toxicological expression profiles, our in vitro assay system could provide important information on toxicity mechanisms. In this study, we treated the rat liver epithelial cell line WB-F344 with phenytoin (PT) or thioacetamide (TA) for 3 and 12 hr. We identified a total of 16,757 differentially expressed genes during the time courses of PT and TA treatments. Specific up-regulated genes at the early time point showed similar expression changes in response to both PT and TA. Also, at 3hr, in vitro PT and TA treatment predominantly gave rise to up-regulation of genes involved in apoptosis, signal transduction and transcriptional regulation. Therefore, these in vitro studies suggest that identifying specific expression patterns at early time points may be valuable in identifying pathways of toxic responses.