Rx-TGx: Toxicogenomic Study Of Pharmaceuticals Using RNA-Seq

The robust transcriptional plasticity of liver mediated through xenobiotic receptors underlies its ability to respond rapidly and effectively to diverse chemical stressors. Thus, drug-induced gene expression changes in liver serve not only as biomarkers of liver injury, but also as mechanistic sentinels of adaptation in metabolism, detoxification and tissue protection from chemicals. Modern RNA sequencing methods offer an unmatched opportunity to quantitatively monitor these processes in parallel and to contextualize the spectrum of dose-dependent stress, adaptation, protection and injury responses induced in liver by drug treatments. Using this approach, we profiled the transcriptional changes in rat liver following daily oral administration of 95 different compounds, many of which are known to be associated with clinical risk for drug induced liver injury (DILI) by diverse mechanisms. Rats received repeted daily dosing of pharmaceuticals; sacrificed 24 hour after the last dose; total RNA extracted from fresh frozen livers.