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GSE39291
Homo sapiens
124 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
The transcriptomic changes induced in the human liver cell line HepG2 by 100M menadione, 200M TBH or 50M H2O2 after treatment for 0.5, 1, 2, 4, 6, 8 and 24h.
Publication Title
Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 560 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
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.
Publication Title
A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 177 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), miRCURY LNA microRNA Array, 5th and 7th generation combined - hsa, mmu & rno (miRBase 19.0)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Sample Metadata Fields
Specimen part, Compound
View Samples- Mus musculus
- 177 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The well-defined battery of in vitro systems applied within chemical cancer risk assessment is often characterised by a high false-positive rate, thus repeatedly failing to correctly predict the in vivo genotoxic and carcinogenic properties of test compounds. Toxicogenomics, i.e. mRNA-profiling, has been proven successful in improving the prediction of genotoxicity in vivo and the understanding of underlying mechanisms. Recently, microRNAs have been discovered as post-transcriptional regulators of mRNAs. It is thus hypothesised that using microRNA response-patterns may further improve current prediction methods. This study aimed at predicting genotoxicity and non-genotoxic carcinogenicity in vivo, by comparing microRNA- and mRNA-based profiles, using a frequently applied in vitro liver model and exposing this to a range of well-chosen prototypical carcinogens. Primary mouse hepatocytes (PMH) were treated for 24 and 48h with 21 chemical compounds [genotoxins (GTX) vs. non-genotoxins (NGTX) and non-genotoxic carcinogens (NGTX-C) versus non-carcinogens (NC)]. MicroRNA and mRNA expression changes were analysed by means of Exiqon and Affymetrix microarray-platforms, respectively. Classification was performed by using Prediction Analysis for Microarrays (PAM). Compounds were randomly assigned to training and validation sets (repeated 10 times). Before prediction analysis, pre-selection of microRNAs and mRNAs was performed by using a leave-one-out t-test. No microRNAs could be identified that accurately predicted genotoxicity or non-genotoxic carcinogenicity in vivo. However, mRNAs could be detected which appeared reliable in predicting genotoxicity in vivo after 24h (7 genes) and 48h (2 genes) of exposure (accuracy: 90% and 93%, sensitivity: 65% and 75%, specificity: 100% and 100%). Tributylinoxide and para-Cresidine were misclassified. Also, mRNAs were identified capable of classifying NGTX-C after 24h (5 genes) as well as after 48h (3 genes) of treatment (accuracy: 78% and 88%, sensitivity: 83% and 83%, specificity: 75% and 93%). Wy-14,643, phenobarbital and ampicillin trihydrate were misclassified. We conclude that genotoxicity and non-genotoxic carcinogenicity probably cannot be accurately predicted based on microRNA profiles. Overall, transcript-based prediction analyses appeared to clearly outperform microRNA-based analyses.
Publication Title
Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Sample Metadata Fields
Specimen part, Compound
View Samples- Mus musculus
- 56 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), miRCURY LNA microRNA Array, 5th and 7th generation combined - hsa, mmu & rno (miRBase 19.0)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Evaluating microRNA profiles reveals discriminative responses following genotoxic or non-genotoxic carcinogen exposure in primary mouse hepatocytes.
Sample Metadata Fields
Specimen part, Compound
View Samples- Mus musculus
- 56 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The study investigated differential gene expression in primary mouse hepatocyte mRNA following 24 and 48 hours of exposure to aflatoxin B1, cisplatin, benzo(a)pyrene, 2,3,7,8-tetrachloordibenzo-p-dioxine, cyclosporin A or Wy-14,643 or their responsive solvent. Three (four for Wy-14,643) biological replicates per compound/solvent.
Publication Title
Evaluating microRNA profiles reveals discriminative responses following genotoxic or non-genotoxic carcinogen exposure in primary mouse hepatocytes.
Sample Metadata Fields
Specimen part, Compound
View Samples- Sus scrofa
- 27 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Sulfur mustard (HD) is a vesicating agent that targets the eyes, skin, and lungs, producing skin burns, conjunctivitis, and compromised respiratory function.
Publication Title
Acute Gene Expression Profile of Lung Tissue Following Sulfur Mustard Inhalation Exposure in Large Anesthetized Swine.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Murine Genome U74A Array (mgu74a)
Description
Inhibition of proteasome degradation pathway has been implicated in neuronal cell death leading to neurodegenerative diseases such as Parkinsons disease and Alzheimers disease. Pharmacological proteasomal inhibitors such as lactacystin can induce apoptosis in cultured mouse cortical neurons through the activation of caspase-3. Furthermore, proteasomal inhibitors are also reported to mediate deleterious alterations in cell cycle regulation, inflammatory processes and protein aggregation and trigger the cell death pathway.
Publication Title
Up-regulation of endoplasmic reticulum stress-related genes during the early phase of treatment of cultured cortical neurons by the proteasomal inhibitor lactacystin.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Projection-dependent ribosome profling from mouse mPFC.
Publication Title
Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Using anti-Argonaute (anti-AGO) antibody co-immunoprecipitation, followed by microarray analyses and downstream bioinformatics, RIP-Chip experiments enable direct analyses of miRNA targets. The analyses support four major findings: (i) RIP-Chip studies correlated with total input mRNA profiling provides more comprehensive information than using either RIP-Chip or total mRNA profiling alone after miRNA transfections; (ii) new data confirm that miR-107 paralogs target coding sequence (CDS) of mRNA; (iii) biochemical and computational studies indicate that the 3 portion of miRNAs plays a role in guiding miR-103/7 to the CDS of targets; and (iv) there are major sequence-specific targeting differences between miRNAs in terms of CDS versus 3-untranslated region targeting, and stable AGO association versus mRNA knockdown. For detailed protocol and for full discussion of the results please see Nelson PT et al, Nucleic Acids Res. 2011 Oct;39(18):8163-72.
Publication Title
Specific sequence determinants of miR-15/107 microRNA gene group targets.
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples