7), and positive regulation of transcription (enrichment score 2.5). The

top clusters for TSC relevant to toxicological processes include cellular response to unfolded protein (enrichment score 4.2; see also cluster 12), cell cycle (enrichment score 3.0), positive regulation of transcription (enrichment score 3.0), response to steroid hormone stimulus (enrichment score 2.8), and positive/negative regulation of apoptosis and cell death (enrichment score 2.0). To investigate early versus downstream effects, functional annotation was applied to significantly differentially expressed genes at the two separate time points. The results are shown GSK3235025 chemical structure in Supplementary Tables 5–8. For cells exposed to MSC at the 6 h time point, the analyses revealed 79 significant (Benjamini–Hochberg-adjusted p < 0.05) terms including those related to transcription activity, DNA binding, and steroid/cholesterol biosynthesis. Four KEGG pathways (MAPK Signaling, Terpenoid Backbone Biosynthesis, p53 Signaling, NOD-like Receptor Signaling) and 1 Biocarta pathway (Oxidative Stress Induced Gene Expression Via Nrf2) were also deemed significant at this time point. At the 6 + 4 h time point, 76 significant terms were identified. These terms included unfolded protein response, and tRNA aminoacylation, as well as steroid/cholesterol

biosynthesis which was found at the 6 h time point. Three KEGG pathways were significant at this time point including Steroid Biosynthesis, Terpenoid Backbone Biosynthesis, and Aminoacyl-tRNA Biosynthesis. Analyses of cells exposed to TSC at the 6 hr time point revealed 67 5-FU datasheet significant terms including

those associated with oxidative stress, cell death, protein unfolding, transcription regulation, DNA binding and cell cycle. In addition, 2 KEGG pathways Cyclin-dependent kinase 3 were significant (MAPK Signaling, p53 Signaling). At the 6 + 4 h time point, 32 GO terms were identified as significant with oxidative stress being the only relevant toxicological endpoint. In addition, only one KEGG pathway (p53 Signaling) was significant. Overall for MSC, the DAVID analyses confirmed many of the significant pathways identified by IPA including steroid biosynthesis, tRNA aminoacylation, inflammation and apoptosis. In addition, the analyses highlighted transcription regulation, DNA binding and unfolded protein response as also significant. For TSC, the DAVID analyses confirmed the significance of IPA pathways related to oxidative stress and cell cycle. As with the MSC, the DAVID analyses also further highlighted the importance of transcription regulation, DNA binding and unfolded protein response, as well as cell death. Transcription regulation and DNA binding were significant terms common to both MSC and TSC at the 6 h time point, whereas no common terms existed for the two condensates at the 6 + 4 h time point.