Profiling of the response of genes in the rat liver to hepatotoxicants
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE15785 | GEO | 2009/04/28
SECONDARY ACCESSION(S): PRJNA116861
REPOSITORIES: GEO
Similar Datasets
Project description:We introduce a new high-throughput transcriptomics (HTTr) platform comprised of a collagen sandwich primary rat hepatocyte culture and the TempO-Seq assay for screening and prioritizing potential hepatotoxicants. We selected 14 chemicals based on their risk of drug-induced liver injury (DILI) and tested them in hepatocytes at two treatment concentrations. HTTr data was generated using the TempO-Seq whole transcriptome and S1500+ assays. The HTTr platform exhibited high reproducibility between technical replicates (r>0.9) but biological replication was greater for TempO-Seq S1500+ (r>0.85) than for the whole transcriptome (r>0.7). Reproducibility between biological replicates was dependent on the strength of transcriptional effects induced by a chemical treatment. Despite targeting a smaller number of genes, the S1500+ assay clustered chemical treatments and produced gene set enrichment analysis (GSEA) scores comparable to those of the whole transcriptome. Connectivity mapping showed a high-level of reproducibility between TempO-Seq data and Affymetrix GeneChip data from the Open TG-GATES project with high concordance between the S1500+ gene set and whole transcriptome. Taken together, our results provide guidance on selecting the number of technical and biological replicates and support the use of TempO-Seq S1500+ assay for a high-throughput platform for screening hepatotoxicants.
2021-09-01 | GSE152128 | GEO
Project description:Zebrafish embryos have been proposed as an attractive alternative model system for hepatotoxicity testing. In this study we determined gene expression responses after exposure to reference hepatotoxicants and controls to identify biomarkers for hepatotoxicity. 188 samples; hepatotoxic compounds at 3 concentrations and with multiple replicates; negative controls at single concentration and with multiple replicates; water (DSW) and 0.2% DMSO vehicle control.
2014-12-16 | E-GEOD-55618 | biostudies-arrayexpress
Project description:Zebrafish embryos have been proposed as an attractive alternative model system for hepatotoxicity testing. In this study we determined gene expression responses after exposure to reference hepatotoxicants and controls to identify biomarkers for hepatotoxicity.
2014-12-16 | GSE55618 | GEO
Project description:The NIEHS data set (endpoint C) was provided by the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (Research Triangle Park, NC, USA). The study objective was to use microarray gene expression data acquired from the liver of rats exposed to hepatotoxicants to build classifiers for prediction of liver necrosis. The gene expression compendium data set was collected from 418 rats exposed to one of eight compounds (1,2-dichlorobenzene, 1,4-dichlorobenzene, bromobenzene, monocrotaline, N-nitrosomorpholine, thioacetamide, galactosamine, and diquat dibromide). All eight compounds were studied using standardized procedures, i.e. a common array platform (Affymetrix Rat 230 2.0 microarray), experimental procedures and data retrieving and analysis processes.
2010-09-25 | GSE24363 | GEO
Project description:Preclinical biomarkers useful for identification of idiosyncratic drugs have not been identified. It is hypothesized that patterns of transcript expression for the hepatotoxicants, including classical and idiosyncratic hepatotoxicants, are similar and the patterns differ from those of non-hepatotoxicants. This experiment is part of the biomarkers study, and focus on two clasical hepatotoxicants: Acetaminophen and Carbon tetrachloride. We have employed whole genome microarray expression profiling to identify liver gene expression changes induced by hepatotoxicants. For the same animal, urinary microRNA profiling were analyzed. APAP and CCl4 both significantly increased the urinary levels of 44 and 28 miRNAs, respectively. In addition, 10 of the increased miRNAs were in common between APAP and CCl4. Computational analysis was used to predict target genes of the 10 shared hepatotoxicant-induced miRNAs. From the same animals, liver gene expression profiling was performed using whole genome microarrays. Eight putative target genes were found to be significantly altered in the liver of APAP and CCl4 treated animals. Acetaminophen induced liver gene expression changes in rats (Six to seven week-old male Sprague-Dawley rats, provided by the US Food and Drug Administration National Center for Toxicological Research (NCTR) breeding colonies, were used for the study.) were measured at 6 hours, 24 hours, 3 days and 7 days after exposure to doses of 0, 100 and 1250 mg/kg. Carbon tetrachloride induced liver gene expression changes in rats were measured at 6 hours, 24 hours and 3 days after exposure to doses of 0, 50 and 2000 mg/kg. Each group has at least 4 animals, total of 96 samples.
2012-03-15 | E-GEOD-32891 | biostudies-arrayexpress
Project description:High-throughput transcriptomics platform for screening hepatotoxicants
| PRJNA638385 | ENA
Project description:Male Sprague Dawley rats were treated orally for 5 days with reference hepatotoxicants, each at a single dose level alpha-naphthylisothiocyanate 100mg/kg (vehicle 5ml/kg corn oil); carbon tetrachloride 1582mg/kg (vehicle 5ml/kg corn oil); methylenedianiline 100mg/kg (vehicle 35% ethanol); acetaminophen 1000mg/kg (vehicle 2ml/kg corn oil); diclofenac 10mg/kg (vehicle 10ml/kg water)
2018-11-06 | GSE122184 | GEO
Project description:Liver tumors in rodents are frequently induced by non-genotoxic carcinogens. These hepatocarcinogens generally activate hepatic nuclear receptors (e.g., CAR and PXR), resulting in a cascade of signals causing modifications in the expression of genes responsible for several processes involved in carcinogenesis. Evaluation of the carcinogenic potential of chemicals is a regulatory requirement but is time-consuming and expensive. Consequently, several short-term in vivo and in vitro approaches, using molecular tools, have been proposed as predictive models for non-genotoxic hepatocarcinogens. The objective of our study was to discriminate between chemicals that are either non-genotoxic hepatocarcinogens or merely hepatotoxicants and also between CAR and PXR modulators on the basis of their gene expression profiles. Thus, we treated rats for seven days with the hepatoxicants, diclofenac and diazepam, or with several CAR and PXR modulators, which were mainly hepatocarcinogens. Different hepatic gene expression profiles were obtained not only between the hepatotoxicants and the non-genotoxic hepatocarcinogens but also between the CAR activators phenobarbital, phenytoin and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene which were grouped together, and the two PXR activators pregnenolone 16α-carbonitrile and clotrimazole. Diethylstilbestrol had an expression profile that was quite distinct from the other PXR activators, suggesting that this compound is certainly not a classic PXR modulator. Moreover, some differences were observed between phenytoin (not considered as a hepatocarcinogen), and the other two CAR activators. Our data therefore indicate that discrimination is possible between hepatocarcinogens and hepatotoxicants, between CAR and PXR modulators and also between compounds within the same class of modulators using a short-term transcriptomic approach. CAR or PXR inducers were administered in suspension to rats (7 weeks old at start of treatment) by oral gavage at a daily dose for 7 consecutive days. Treatment-related changes in gene expression were determined in the liver using whole genome oligonucleotide microarrays.
2013-07-31 | E-GEOD-39350 | biostudies-arrayexpress
Project description:Liver tumors in rodents are frequently induced by non-genotoxic carcinogens. These hepatocarcinogens generally activate hepatic nuclear receptors (e.g., CAR and PXR), resulting in a cascade of signals causing modifications in the expression of genes responsible for several processes involved in carcinogenesis. Evaluation of the carcinogenic potential of chemicals is a regulatory requirement but is time-consuming and expensive. Consequently, several short-term in vivo and in vitro approaches, using molecular tools, have been proposed as predictive models for non-genotoxic hepatocarcinogens. The objective of our study was to discriminate between chemicals that are either non-genotoxic hepatocarcinogens or merely hepatotoxicants and also between CAR and PXR modulators on the basis of their gene expression profiles. Thus, we treated rats for seven days with the hepatoxicants, diclofenac and diazepam, or with several CAR and PXR modulators, which were mainly hepatocarcinogens. Different hepatic gene expression profiles were obtained not only between the hepatotoxicants and the non-genotoxic hepatocarcinogens but also between the CAR activators phenobarbital, phenytoin and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene which were grouped together, and the two PXR activators pregnenolone 16α-carbonitrile and clotrimazole. Diethylstilbestrol had an expression profile that was quite distinct from the other PXR activators, suggesting that this compound is certainly not a classic PXR modulator. Moreover, some differences were observed between phenytoin (not considered as a hepatocarcinogen), and the other two CAR activators. Our data therefore indicate that discrimination is possible between hepatocarcinogens and hepatotoxicants, between CAR and PXR modulators and also between compounds within the same class of modulators using a short-term transcriptomic approach.
2013-07-31 | GSE39350 | GEO
Project description:The NIEHS data set (endpoint C) was provided by the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (Research Triangle Park, NC, USA). The study objective was to use microarray gene expression data acquired from the liver of rats exposed to hepatotoxicants to build classifiers for prediction of liver necrosis. The gene expression compendium data set was collected from 418 rats exposed to one of eight compounds (1,2-dichlorobenzene, 1,4-dichlorobenzene, bromobenzene, monocrotaline, N-nitrosomorpholine, thioacetamide, galactosamine, and diquat dibromide). All eight compounds were studied using standardized procedures, i.e. a common array platform (Affymetrix Rat 230 2.0 microarray), experimental procedures and data retrieving and analysis processes. For each compound, four to six male, 12 week old F344 rats were exposed to a low dose, mid dose(s) and a high dose of the toxicant and sacrificed at 6, 24 and 48 hrs later. At necropsy, liver was harvested for RNA extraction, histopathology, and clinical chemistry assessments.
2010-09-25 | E-GEOD-24363 | biostudies-arrayexpress