HepG2 cells exposed to pesticides and related compounds (part 2)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Rachel Cavill
PROVIDER: E-MTAB-3509 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:HepG2 cells were exposed for 24 hours to the IC20 (72hr MTT) dose of various pesticides and related compounds selected from the EPA Toxcast phase 1 set. This is the first part of two batches of experiments, these experiments were used as a training set and the second batch as a validation set.
2019-06-20 | E-MTAB-3508 | biostudies-arrayexpress
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2021-09-09 | PXD020666 | Pride
Project description:The lack of accurate in vitro assays for predicting in vivo toxicity of chemicals together with new legislations demanding replacement and reduction of animal testing has triggered the development of alternative methods. This study aimed at developing a transcriptomics-based in vitro prediction assay for in vivo genotoxicity. The transcriptomics changes induced in the human liver cell line HepG2 by 34 compounds after treatment for 12h, 24h and 48h were used for the selection of gene-sets that can discriminate between in vivo genotoxins (GTX) and in vivo non-genotoxins (NGTX). By combining publicly available results for these chemicals from standard in vitro genotoxicity studies with transcriptomics, we developed several prediction models. These models were validated by means of an additional set of 28 chemicals. The study investigated differential gene expression in HepG2 cell line mRNA following 12 hours of exposure to 34 different compounds and their solvents; 24 and 48 hours of exposure to 62 different compounds and their solvents. Three biological replicates per compound/solvent. In total 560 arrays .
2012-08-02 | E-GEOD-28878 | biostudies-arrayexpress
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2015-10-01 | E-MTAB-3324 | biostudies-arrayexpress
Project description:In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery During drug discovery and development, the early identification of adverse effects is expected to reduce costly late stage failures of candidate drugs. As risk/safety assessment takes place rather late during the development process and due to the limited predictivity of animal models to the human situation, modern unbiased high-dimensional biology read-outs are sought, such as molecular signatures of in vivo response using high-throughput cell-based assays. In this theoretical proof-of-concept we provide findings of an in-depth exploration of a single chemical core structure. Via transcriptional profiling we identified a subset of close analogs which commonly down-regulate tubulin genes across cellular contexts, suggesting possible spindle poison effects. Confirmation via a qualified toxicity assay (in vitro micronucleus test) and the identification of a characteristic aggregate-formation phenotype via exploratory high content imaging validated the inititial findings. SAR analysis triggered the synthesis of a new set of compounds and allowed us to extend the series showing the genotoxic effect. We demonstrate the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery. We share our thoughts on how this approach may be incorporated into drug development strategies. Cells were cultured using standard protocols, seeded in 96 well plate, cultured for 8 hours before treatment with a number of inhouse synthesized compounds. The treatments represent different chemical structures/small molecules that have been synthesized in the context of developing a new drug targeting PDE10A.
2015-12-31 | E-GEOD-70611 | biostudies-arrayexpress
Project description:The transcriptomics changes induced in the human liver cell line HepG2 by Cyclosporin A after treatment for 12h, 24h, 48h and 72h The study investigated differential gene expression in HepG2 cell line mRNA following 12, 24, 48 and 72 hours of exposure to Cyclosporin A and solvent. Three biological replicates per compound/solvent. In total 36 arrays.
2015-01-27 | E-GEOD-45635 | biostudies-arrayexpress
Project description:HepG2 cells (human liver hepatocarcinoma) were exposed for 6 different time points (6,12,18,24,36 and 48h) to Benzo[a]pyrene (BaP) in duplicate. Total RNAs were ribo-depleted and sequenced on an Illumina Hiseq2000 in pair-end 100 bp reads. One of the duplicates for BaP-treated sample at the 24 hour time point was found to have a minor fastq file integrity issue and was removed from this data set as a precaution.
2015-08-02 | E-MTAB-3292 | biostudies-arrayexpress
Project description:Whole-genome transcriptome measurements are pivotal for characterizing carcinogenic mechanisms of chemicals and predicting toxic classes, such as genotoxicity, from in vitro and in vivo assays. DNA microarrays have evolved as the gold standard for this purpose. In recent years deep sequencing technologies have been developed that hold the promise of measuring the transcriptome with RNA-seq in a more accurate and unbiased manner than microarrays. So far, however, few applications have been published that assess the performance of RNA-seq within a toxicogenomics context. Here, we applied RNA-seq for the characterization of the in vitro transcriptomic responses in HepG2 cells upon exposure to benzo[a]pyrene (BaP), a well-known DNA damaging carcinogen. We demonstrate the performance of RNA-seq with respect to the identification of differentially expressed genes and associated pathways, in comparison with microarray technology. RNA-seq data generates more complete and thus accurate data on differentially expressed genes and affected pathways than microarrays. Additionally, we highlight the potential of RNA-seq for characterizing mechanisms related to alternative splicing and thereby gathering new information. Exposure to BaP alters the isoform distribution for many genes, including regulators of cell death and DNA repair such as TP53, BCL2 and XPA, which are relevant for genotoxic responses. Finally, we demonstrate that RNA-seq enables to investigate allele-specific gene expression, although no changes for that could be observed. Our results provide evidence that RNA-seq is a powerful tool for toxicology which, compared to microarrays, is capable of adding valuable information at the transcriptome level for characterizing toxic effects caused by chemicals. Examination of 2 biological replicates at 2 different timepoints
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