Assessing Concordance of Drug-Induced Transcriptional Response in Rodent Liver and Cultured Hepatocytes
A) Distribution of average absolute eigengene scores for 4182 rat liver drug treatments from DM and TG, and 6 baseline expression comparisons of control samples (shown in red text in the inset). The solid and dashed vertical lines denote the median and 90th percentile values for avg. abs. EG. Rat liver histology sections: B) Unaffected liver. A central vein (asterisk) and small portal triad (arrowhead) are marked. Mild hepatocellular glycogen (recognized by cytoplasmic pallor) is apparent in the periportal region. C) Liver histology 1 day after the last dose of methapyrilene administered at 100 mg/kg for 29 days. Biliary hyperplasia (to the left of the arrows), correlating with increased alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) activities (S7 Table), and hepatocellular apoptosis/single cell necrosis (arrowheads) are noted. Hepatocytes in the right side of the image are hypertrophied and exhibit prominent anisonucleosis. D) Liver histology 1 day after bortezomib administration at 1 mg/kg. Acute hepatocellular necrosis (left of the arrows) and mild hepatocellular vacuolation (arrowheads) are noted. Images were extracted from the Open TG-GATES website (http://toxico.nibiohn.go.jp/english/).