AOPs Including This Stressor
Events Including This Stressor
|User term||DTXID||Preferred name||Casrn||jchem_inchi_key||indigo_inchi_key|
1. CITCO was identified as a CAR activator using an in vitro fluorescence-based CAR activation assay, and incubation of primary human hepatocytes isolated from two donors with 1 µM CITCO for 48 h resulted in the transcriptional upregulation of selected genes involved in xenobiotic metabolism, including the prototypical CAR target gene CYP2B6 (Maglich et al., 2003).
2. Genome-wide transcriptional profiling performed on primary human hepatocytes isolated from six individual donors exposed to 1 µM CITCO for 24 h resulted in the modulation of genes primarily involved in xenobiotic metabolism including CYP2B6, CYP2B7P1 and CYP2A7 (Kandel et al., 2016).
3. WT and hCAR-KO HepaRG cells (human hepatic cell line) were exposed to vehicle or 1 µM CITCO for 24 h, and mRNA was subjected to global gene expression analysis. Comparative analyses identified both previously identified CAR-responsive genes and novel genes that were associated with hCAR activation (Li et al., 2015). These experiments also demonstrated that CITCO achieved CYP2B6 induction predominantly via hCAR activation, whereas phenobarbital induced CYP2B6 by both hCAR and hPXR activation. Many of the genes that were differentially expressed via hCAR activation reflected an inhibition of cell cycle progression (i.e. cell proliferation) in these human HepaRG cultures. These cell cycle/proliferation related pathways repressed by hCAR activation included the TGF-β, p53 and Jak-STAT pathways. In addition, the known role of activators of mCAR in mouse liver for controlling lipogenesis via gene expression changes was not apparent in human HepRG cells after treatments with known hCAR activators.
4. In contrast to the results in HepaRG cells (above), immortalized human hepatocytes (IHH) incubated with 1 µM CITCO for 48 h resulted in the induction of prototypical CAR-responsive gene CYP2B6, and genes/transcription factors involved in lipid metabolism that could suggest a lipogenic response in human liver (Marmugi et al., 2016).