Figure 3

Molecular phenotyping of drug response in primary human hepatocytes. (A) Principal comment analysis of differential gene expression induced by Diclofenac and the test compound in three primary human hepatocyte cell lines. (B) Differential expression of FGF21, GDF15, ATF3, and EGR1 induced by Diclofenac and test compound. The genes belong to an early induced stress-response network that is associated with cytotoxicity in vitro and in vivo. Average expression levels are expressed as log2-transformed copies per million reads (cpm). Error bars indicate standard deviation of two or three independent biological replicates. (C) Hypoxia signaling pathway reporter genes with dose-dependent gene expression profiles identified by AmpliSeq-RNA. Dots indicate mean expression of replicates. (D) Intracellular ATP abundance and LDH leakage in test compound treated cells measured by in vitro assays. Vertical bars indicate percentage (%) of average values of the control condition. Error bars indicate standard deviation of two or three independent biological replicates.