A Genomics-Based Analysis of Relative Potencies of Dioxin-Like Compounds in Primary Rat Hepatocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Craig Rowlands
PROVIDER: E-GEOD-49473 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Transcriptional profiling of primary rat hepatocytes exposed to high and low doses of three compounds, as well as untreated cells. All samples were co-hybridized with DMSO controls. A direct two-color experiment design, with each treated sample co-hybridized with a DMSO control. Hepatocytes derived from two animals were used as biological replicates. Four microarrays were completed for each chemical/dose combination. The four replicate arrays represent two dye-swapped microarrays for each of the two animals.
2011-11-01 | E-GEOD-29095 | biostudies-arrayexpress
Project description:The human and mouse aryl hydrocarbon receptor (hAHR and mAHRb) share limited (58%) transactivation domain sequence identity. Compared to the mAHRb allele, the hAHR displays 10-fold lower relative affinity for prototypical ligands such as 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). However, in previous studies we have demonstrated that the hAHR can display a higher relative ligand binding affinity than the mAHRb for specific AHR ligands such as indirubin. Each receptor has also been shown to differentially recruit LXXLL co-activator-motif proteins and to utilize different TAD subdomains in gene transactivation. Using hepatocytes isolated from C57BL6/J mice (Ahrb/b) and AHRTtr transgenic mice which express hAHR protein specifically in hepatocytes, we investigated whether the hAHR and mAHRb differentially regulate genes. Microarray and quantitative-PCR analysis of Ahrb/b and AHRTtr primary-mouse hepatocytes treated with 10 nM TCDD revealed that a number of established AHR target genes such as Cyp1a1 and Cyp1b1 are significantly induced by both receptors. Remarkably, of the 1752 genes induced by mAHRb and 1186 genes induced by hAHR, only 265 genes (<10%) were significantly activated by both receptors in response to TCDD. Conversely of the 1100 and 779 genes significantly repressed in mAHRb and hAHR hepatocytes respectively, only 462 (<25%) genes were significantly repressed by both receptors in response to TCDD treatment. Genes identified as differentially expressed are known to be involved in a number of biological pathways, including cell proliferation and inflammatory response which suggests that compared to the mAHRb, the hAHR may play contrasting roles in TCDD-induced toxicity and endogenous AHR-mediated gene regulation. Experiment Overall Design: Isolated mouse hepatocytes from wild type and treated with 10nM TCDD for 6h were analyzed. 1 array per mouse (3 mice per treatment group) was used.GeneChip® Operating Software (Affymetrix) was utilized to preprocess CAB/CEL files generated from the 12 scanned microarrays which represented hepatocytes isolated from one mouse each. Data quality was initially assessed by checking the array image, B2 oligo performance, average background to noise ratios, poly-A controls, hybridization controls and the 3' to 5' probe-set ratios for control genes (e.g. Ã-actin or GAPDH). Microarray data was normalized using Probe Logarithmic Intensity Error Approximation PLIER-MM algorithm (Affymetrix Expression Console⢠Software 1.1). Normalized microarray data outputs from TCDD and control treated Ahrb/band AHRTtr hepatocytes were compared for differential expression using Significance Analysis of Microarrays (SAM, version 2.23A (Pan 2002; Tusher et al. 2001)) with 100 permutations, KNN-10.
2009-09-13 | E-GEOD-17925 | biostudies-arrayexpress
Project description:This study provides an evaluation of changes in gene expression associated with acetominophen treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses (500 uM and 5 mM) of acetominophen and 1% DMSO vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis. This series is part of a SuperSeries in which primary rat hepatocytes were treated with two doses of ten chemical compounds (and corresponding vehicle controls) for 24 and 48 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported. Time Course/Dose Response
2012-08-28 | E-GEOD-40336 | biostudies-arrayexpress
Project description:This study provides an evaluation of changes in gene expression associated with chlorpromazine HCl treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses (0.8 uM and 20 uM) of chlorpromazine HCl and 1% DMSO vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis. This series is part of a SuperSeries in which primary rat hepatocytes were treated with two doses of ten chemical compounds (and corresponding vehicle controls) for 24 and 48 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported. Time Course/Dose Response
2012-08-28 | E-GEOD-40341 | biostudies-arrayexpress
Project description:This study provides an evaluation of changes in gene expression associated with clofibrate treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses (60 uM and 1 mM) of clobibrate and 1% DMSO vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis. This series is part of a SuperSeries in which primary rat hepatocytes were treated with two doses of ten chemical compounds (and corresponding vehicle controls) for 24 and 48 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported. Time Course/Dose Response
2012-08-28 | E-GEOD-40344 | biostudies-arrayexpress
Project description:This study provides an evaluation of changes in gene expression associated with dioctyl phthalate treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses (250 uM and 1 mM) of dioctyl phthalate and 1% DMSO vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis. This series is part of a SuperSeries in which primary rat hepatocytes were treated with two doses of ten chemical compounds (and corresponding vehicle controls) for 24 and 48 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported. Time Course/Dose Response
2012-08-28 | E-GEOD-40337 | biostudies-arrayexpress
Project description:This study provides an evaluation of changes in gene expression associated with beta-naphthaflavone treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses 1 uM and 100 mM) of beta-naphthaflavone and 1% DMSO vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis. This series is part of a SuperSeries in which primary rat hepatocytes were treated with two doses of ten chemical compounds (and corresponding vehicle controls) for 24 and 48 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported. Time Course/Dose Response
2012-08-28 | E-GEOD-40340 | biostudies-arrayexpress
Project description:This study provides an evaluation of changes in gene expression associated with methapyrilene treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses (3 uM and 100 uM) of methaphyriline and 1% DMSO vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis. This series is part of a SuperSeries in which primary rat hepatocytes were treated with two doses of ten chemical compounds (and corresponding vehicle controls) for 24 and 48 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported. Time Course/Dose Response
2012-08-28 | E-GEOD-40347 | biostudies-arrayexpress
Project description:This study provides an evaluation of changes in gene expression associated with WY-14643 treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses 8 uM and 200 uM) of WY-14643 and 1% DMSO vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis. This series is part of a SuperSeries in which primary rat hepatocytes were treated with two doses of ten chemical compounds (and corresponding vehicle controls) for 24 and 48 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported. Time Course/Dose Response
2012-08-28 | E-GEOD-40346 | biostudies-arrayexpress
Project description:This study provides an evaluation of changes in gene expression associated with diisononyl phthalate treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses (25 mM and 100 mM) of diisononyl phthalate and 1% DMSO vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis. This series is part of a SuperSeries in which primary rat hepatocytes were treated with two doses of ten chemical compounds (and corresponding vehicle controls) for 24 and 48 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported. Time Course/Dose Response
2012-08-28 | E-GEOD-40342 | biostudies-arrayexpress