ArticleToxicology and applied pharmacology2008
Expression profiling of interindividual variability following xenobiotic exposures in primary human hepatocyte cultures.
Article in Toxicology and applied pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Characterization of peroxisome proliferator-activated receptor alpha--independent effects of PPARalpha activators in the rodent liver: di-(2-ethylhexyl) phthalate also activates the constitutive-activated receptor.Toxicological sciences : an official journal of the Society of Toxicology · 2010Pooled it
- Restored glyoxylate metabolism after AGXT gene correction and direct reprogramming of primary hyperoxaluria type 1 fibroblasts.iScience · 2024Article
- Guide to the Assessment of Mature Liver Gene Expression in Stem Cell-Derived Hepatocytes.Stem cells and development · 2019Article
- Through the Looking Glass:Applied in vitro toxicology · 2018Review
- Regulation of Cytochrome P450 2B10 (CYP2B10) Expression in Liver by Peroxisome Proliferator-activated Receptor-β/δ Modulation of SP1 Promoter Occupancy.The Journal of biological chemistry · 2016Article
- Activation of the Constitutive Androstane Receptor by Monophthalates.Chemical research in toxicology · 2016Article
- Evaluation of a novel PXR-knockout in HepaRGPharmacology research & perspectives · 2016Article
- Intronic DNA elements regulate Nrf2 chemical responsiveness of the human microsomal epoxide hydrolase gene (EPHX1) through a far upstream alternative promoter.Biochimica et biophysica acta · 2014Article
- Proteasomal interaction as a critical activity modulator of the human constitutive androstane receptor.The Biochemical journal · 2014Article
- Aryl hydrocarbon receptor activation by dioxin targets phosphoenolpyruvate carboxykinase (PEPCK) for ADP-ribosylation via 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP-ribose) polymerase (TiPARP).The Journal of biological chemistry · 2013Article
- The orphan nuclear receptor DAX-1 functions as a potent corepressor of the constitutive androstane receptor (NR1I3).Molecular pharmacology · 2012Article
- Changes in the proteomic profile of adipose tissue-derived mesenchymal stem cells during passages.Proteome science · 2012Article
- Comparative gene expression profiles induced by PPARγ and PPARα/γ agonists in human hepatocytes.PloS one · 2011Article
- Selective phthalate activation of naturally occurring human constitutive androstane receptor splice variants and the pregnane X receptor.Toxicological sciences : an official journal of the Society of Toxicology · 2011Article
- The hepatitis B virus HBx protein modulates cell cycle regulatory proteins in cultured primary human hepatocytes.Virus research · 2011Article
- Evaluation of an in vitro toxicogenetic mouse model for hepatotoxicity.Toxicology and applied pharmacology · 2010Article
- Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver.PPAR research · 2010Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
To examine the magnitude of human variability across the entire transcriptome after chemical challenge, we profiled gene expression responses to three different prototypic chemical inducers in primary human hepatocyte cultures from ten independent donors. Correlation between basal expression in any two hepatocyte donors ranged from r(2) values of 0.967 to 0.857, and chemical treatment tended to negatively impact correlation between donors. Including anticipated target genes, 10,812, 8373, and 7847 genes were changed in at least one donor by Aroclor 1254 (A1254), di(2-ethylhexyl) phthalate (DEHP), and phenobarbital (PB), respectively. A subset of these gene targets (n=41) were altered with a high level of reproducibility in at least 9 donors, gene responses that correlated well with literature-reported mechanism of action. Filtering responses to the level of gene subsets clarified the biological impact associated with the respective chemical effectors, in lieu of substantial interindividual variation among donor responses. In these respects, the use of hierarchical clustering methods successfully grouped seven of the ten donors into chemical-specific rather than donor-specific clusters. However, at the whole-genome level, the magnitude of conserved gene expression changes among donors was surprisingly small, with fewer than 50% of the gene responses altered by a single chemical conserved in more than one donor. The use of higher level descriptors, such as those defined by the PANTHER classification system, may enable more consistent categorization of gene expression changes across individuals, as increased reproducibility was identified using this method.
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