Toxicogenomics directory of rat hepatotoxicants in vivo and in cultivated hepatocytes
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PROVIDER: PRJNA490737 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptomics is developing into an invaluable tool in toxicology. The aim of this study was, using a transcriptomics approach, to identify genes that respond similarly to chemicals (including drugs and industrial compounds) in both rat liver in vivo and in cultivated hepatocytes, which are up- or downregulated by many different test compounds. For this purpose, we analyzed Affymetrix gene array data from 162 compounds that were previously tested in a concentration-dependent manner in rat livers in vivo and rat hepatocytes cultivated in sandwich culture. These data were obtained from the Japanese Toxicogenomics (TGP) and North-Rhine-Westphalian (NRW) data sets, which consist of 138 and 29 compounds, respectively, and have 5 mutual compounds between them. The in vitro gene array data from the NRW data set were generated in the present study, while TGP is publicly available. For each of the data sets, the overlap between up- or down-regulated genes in vitro and in vivo was identified, further named in vitro-in vivo consensus genes. Interestingly, an overlap of in vivo-in vitro consensus genes was obtained between both data sets, which were 21-times (up-regulated genes) or 12-times (down-regulated genes) en-riched compared to random expectation. This is remarkable since the TGP and NRW data sets contained only five mutual compounds. Finally, the genes in the TGP and NRW overlap were used to identify the upregulated genes with the highest com-pound coverage, resulting in a 7-gene set of Cyp1a1, Ugt2b1, Cdkn1a, Mdm2, Aldh1a1, Cyp4a3, and Ehhad. This 7-gene set was then successfully tested with structural analogues of valproic acid that are not present in the TGP and NRW data sets. In conclusion, the 7-gene set identified in the present study responds similarly in vitro and in vivo and is induced by a wide range of different chemicals. Despite these results, transcriptomics with cultivated rat hepatocytes remains a challenge, because many genes are up- or downregulated by the culture conditions, respond differently to test compounds in vitro and in vivo, and shows a higher variability in the in vitro system compared to the corresponding in vivo data. The raw data for the TGP study are available at https://toxico.nibiohn.go.jp/ For the normalization of the entire set of expression arrays, the RMA algorithm was used. The results are summarized in the publicly available toxicotranscriptomics directory (http://wiki.toxbank.net/toxicogenomics-map/).
2018-09-14 | GSE119933 | GEO
Project description:We investigated the effects of the flutamide (FLU) -induced liver injury in primary rat hepatocytes using our liver microfluidic biochips. Flutamide is used a non-steroidal anti-androgenic drug. Two flutamide concentrations, 10M-BM-5M and 100M-BM-5M, were used to expose the hepatocytes for 24h under perfusion. Primary rat hepatocytes were cultivated in microfluidic biochips and treated with 10 and 100M-BM-5M of flutamide for 24h
2013-12-01 | E-GEOD-44317 | biostudies-arrayexpress
Project description:A toxicogenomics approach was used to qualitatively and quantitatively compare gene expression changes in rat primary hepatocytes exposed to 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) or 2,3,7,8-tetrachlorodibenzofuran (TCDF). Hepatocytes from five individual rats were exposed for 24 hours to 11 concentrations of each chemical ranging from 0.00001 nM to 100 nM and a vehicle control.
2014-01-01 | GSE49473 | GEO
Project description:DrugMatrix is a comprehensive rat toxicogenomics database and analysis tool developed to facilitate the integration of toxicogenomics into hazard assessment. Using the whole genome and a diverse set of compounds allows a comprehensive view of most pharmacological and toxicological questions and is applicable to other situations such as disease and development. Complete Drug Matrix dataset for primary rat hepatocytes. Cells were exposed to toxicants in culture medium and harvested after 0.67 or 1 day.
2014-05-27 | E-GEOD-57805 | biostudies-arrayexpress
Project description:A toxicogenomics approach was used to qualitatively and quantitatively compare the gene expression changes in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hepatocytes from five individual rats and five individual humans were exposed for 24 hours to 11 concentrations of TCDD ranging from 0.00001 nM to 100 nM and a vehicle control. Gene expression changes were analyzed using whole genome microarrays.
2012-02-03 | GSE34250 | GEO
Project description:DrugMatrix is a comprehensive rat toxicogenomics database and analysis tool developed to facilitate the integration of toxicogenomics into hazard assessment. Using the whole genome and a diverse set of compounds allows a comprehensive view of most pharmacological and toxicological questions and is applicable to other situations such as disease and development. Complete Drug Matrix dataset for rat hepatocytes. Approximately 600 different compounds were profiled in up to 8 different rat tissues by obtaining tissue samples from test compound-treated and vehicle control-treated rats in biological triplicates for gene expression analysis after 0.25, 1, 3, and 5 days of exposure with daily dosing. In a few studies (1.8%), 7 days of exposure was substituted for 5 days of exposure. Samples were hybridized to CodeLink RU1 10K rat arrays (Amersham Biosciences).
2014-08-18 | E-GEOD-59906 | biostudies-arrayexpress
Project description:A toxicogenomics approach was used to qualitatively and quantitatively compare gene expression changes in rat primary hepatocytes exposed to 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) or 2,3,7,8-tetrachlorodibenzofuran (TCDF). Hepatocytes from five individual rats were exposed for 24 hours to 11 concentrations of each chemical ranging from 0.00001 nM to 100 nM and a vehicle control. 115 microarrays representing primary hepatocytes from 5 rats, each exposed to 11 doses of each chemical (PeCDF and TCDF) and vehicle controls. Arrays were completed with a one-color design.
2014-01-01 | E-GEOD-49473 | biostudies-arrayexpress
Project description:A toxicogenomics approach was used to qualitatively and quantitatively compare the gene expression changes in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hepatocytes from five individual rats and five individual humans were exposed for 24 hours to 11 concentrations of TCDD ranging from 0.00001 nM to 100 nM and a vehicle control. Gene expression changes were analyzed using whole genome microarrays.
2012-02-03 | GSE34249 | GEO
Project description:Toxicogenomics databases are useful for understanding biological responses in individuals because they are derived from well-controlled experiments and include a diverse spectrum of biological responses. Although these databases contain no information regarding immune cells in the liver, which are important in the progression of liver injury, deconvolution that estimates cell-type proportions from bulk transcriptome could add information regarding immune cell trafficking to the database. However, deconvolution has been mainly applied to humans and mice and less often to rats, which are the main target of toxicogenomics databases. Here, we developed a deconvolution method for rats and established a methodology to obtain information regarding immune cells from toxicogenomics databases. The contributions of this work are three-fold. First, we obtained the gene expression profiles of various rat immune cells necessary for deconvolution and constructed a dataset; second, we compared the accuracy of models based on human and mouse datasets and showed the impact of species differences on deconvolution; third, we showed that rat deconvolution could retrieve information regarding immune cell trafficking from toxicogenomics databases. Correspondence: Tadahaya Mizuno
2023-08-15 | GSE239996 | GEO
Project description:The transcriptional response to interferon alpha is cell type specific. To data, majority of investigations of interferon alpha induced gene expression have been made using immortalized or transformed cell lines underlining interferon's importance for treatment of cancer but omitting physiological relevance. Here in we have determined gene expression change in primary culture of hepatocytes after interferon alpha treatment. We used Affymetrix Rat Genome 230 2 microarrays to determine gene expression profiles in primary rat hepatocytes after interferon alpha treatment and untreated cells. Primary hepatocytes were chosen because they are most relevant to physiological state in intact liver. Hepatocytes was isolated from rat liver using collagenase treatment procedure and purified on percoll gradient. Next day after isolation primary hepatocytes culture was cultivated with (or without) 250u/ml rat interferon alpha for 3 and 6 hours. Experiment was performed in 3 biological replicates. cRNA preparation was performed according manufacturer's recommendation from 5ug of total RNA and gene expression profiles were determined.
2013-07-15 | E-GEOD-43723 | biostudies-arrayexpress