Toxicogenomic profiling in the whole zebrafish embryo after exposure to reference hepatotoxicants.
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE55618 | GEO | 2014/12/16
SECONDARY ACCESSION(S): PRJNA240229
REPOSITORIES: GEO
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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:The zebrafish is as a powerful vertebrate model system for modeling human disease including liver pathology. In ZFE, hepatic responses can be expected after exposure to hepatotoxicants, because hepatocytes are present from 36-hpf and at 72-hpf the liver is fully functioning. These characteristics make the whole ZFE an attractive alternative model for compound-induced hepatotoxicity screening. Therefore, the main objective of this study is to further strengthen the applicability of whole ZFE as an alternative model for hepatotoxicity testing, with a special focus on the ability to identify gene expression responses in whole ZFE that are suggestive of hepatotoxicity. Deep sequence technology is applied to assess whether hepatotoxicity-specific transcripts that are identified in livers of hepatotoxicant treated adult zebrafish can be detected in whole ZFE as well.
2015-05-15 | GSE38042 | GEO
Project description:The zebrafish is as a powerful vertebrate model system for modeling human disease including liver pathology. In ZFE, hepatic responses can be expected after exposure to hepatotoxicants, because hepatocytes are present from 36-hpf and at 72-hpf the liver is fully functioning. These characteristics make the whole ZFE an attractive alternative model for compound-induced hepatotoxicity screening. Therefore, the main objective of this study is to further strengthen the applicability of whole ZFE as an alternative model for hepatotoxicity testing, with a special focus on the ability to identify gene expression responses in whole ZFE that are suggestive of hepatotoxicity. Deep sequence technology is applied to assess whether hepatotoxicity-specific transcripts that are identified in livers of hepatotoxicant treated adult zebrafish can be detected in whole ZFE as well. Whole zebrafish embryo and adult zebrafish are exposed for 48 hours to human hepatotoxicants. Afterwards, the adult liver is dissected and snap frozen untill processed for RNA isolation. The whole zebrafish embryos are pooled, one sample consists of 15 embryos, and are also snap frozen untill processed for RNA isolation. For every sample RNA is isolated according to the protocol of de Jong et al (2009). and then equal amounts of every sample is pooled. The two pools (one for the adult zebrafish liver, the other for the whole zebrafish embryo) are sequenced.
2015-05-15 | E-GEOD-38042 | biostudies-arrayexpress
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: Not available
| S-EPMC2246301 | biostudies-literature
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:Expression Data from Liver of Rats Dosed with Reference Hepatotoxicants (Microarray)
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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:This data set comprises of the standardized experimental design for the microarray gene expression data derived from the rat liver (target tissue) after treatment with eight known hepatotoxicants (at multiple time points and doses with multiple biological replicates and a fluor-flip for each biological sample).
2009-04-28 | GSE15785 | GEO