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GSE84250
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), (imblegenhumandnamethylation2.1mdeluxepromoterarray[100929hg19deluxeprommethhx1)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Valproic acid (VPA) is a very potent anti-cancer and neuro-protective drug. However, exposure to VPA may cause accumulation of lipids in the liver which could result in the development of steatosis. As VPA is a fatty acid analogue, most of the performed studies focus on inhibition of the mitochondrial b-oxidation pathway as the possible mode of action. However, investigations exploring the contribution of other processes in particular by using whole genome studies in a relevant human liver model are limited. Furthermore, the contribution of gene expression regulation by DNA methylation changes and/or miRNA changes is hardly known. Therefore, in the present study, we investigated the effect of repetitive VPA exposure on primary human hepatocytes (PHH) on whole genome gene expression-, DNA methylation-, and miRNA changes, using microarrays and integrated data analyses. PHH were exposed to a non-cytotoxic dose of 15 mM VPA for 5 days daily thereby inducing accumulation of lipids. Part of the PHH was left untreated for an additional 3 days in order to study the persistence of changes. VPA modulated the expression of a number of nuclear receptors and their target genes, leading to disturbed fatty acid metabolism and - uptake, ultimately leading to accumulation of triglycerides in the liver which is the key event leading to steatosis. Part of the gene expression changes was epigenetically regulated. Furthermore, after terminating the treatment, the expression and DNA methylation changes of several genes remained persistent, indicating a permanent change in the PHH, causing steatosis development to continue and/or making the PHH more sensitive for steatosis development during a subsequent exposure.
Publication Title
Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction.
Sample Metadata Fields
Specimen part, Treatment
View Samples- 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- Homo sapiens
- 77 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Understanding toxicity pathways of engineered nanomaterials (ENM) has recently been brought forward as a key step in 21st century ENM risk assessment. Molecular mechanisms linked to phenotypic end points is a step towards the development of toxicity tests based on key events, which may allow for grouping of ENM according to their mechanisms of action. This study identified molecular mechanisms underlying mitochondrial dysfunction in human bronchial epithelial BEAS 2B cells following exposure to one of the most studied multi-walled carbon nanotubes (MWCNTs; Mitsui-7). Asbestos was used as a positive control and a non-carcinogenic glass wool material was included as a negative fibre control. Decreased mitochondrial membrane potential (MMP) was observed for MWCNTs at a biologically relevant dose (0.25 g/cm2) and for asbestos at 2 g/cm2, but not for glass wool. Extensive temporal transcriptomic and microRNA expression analyses identified a 330-gene signature related to MWCNT- and asbestos-induced MMP. Fourty-nine of the MMP-associated genes showed highly similar expression patterns over time (six time points) and the majority was found to be regulated by two transcription factors strongly involved in mitochondrial homeostasis, APP and NRF1. In addition, four miRNAs were associated with MMP and one of them, miR-1275, was found to negatively correlate with a large part of the MMP-associated genes. Cellular processes such as gluconeogenesis, glucose metabolism, mitochondrial LC-fatty acid -oxidation and spindle microtubule function were enriched among the MMP-associated genes and miRNAs. These results are expected to be useful in the identification of key events in ENM-related toxicity pathways for the development of molecular screening techniques.
Publication Title
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), (imblegenhumandnamethylation2.1mdeluxepromoterarray[100929hg19deluxeprommethhx1)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma.
Sample Metadata Fields
Specimen part, Disease, Compound
View Samples- Homo sapiens
- 6 Downloadable Samples
- (imblegenhumandnamethylation2.1mdeluxepromoterarray[100929hg19deluxeprommethhx1), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The study investigated differential gene expression, microRNA expression and DNA methylation changes in a pool of primary human hepatocyte RNA and DNA following 5 days of repetitive exposure to a low (LD) or moderate (MD) dose of aflatoxin B1 or DMSO. Three biological replicates per compound/solvent.
Publication Title
Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma.
Sample Metadata Fields
Specimen part, Compound
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic exposure to aflatoxin B1 (AFB1) has, in certain regions in the world, been strongly associated with the development of hepatocellular carcinoma (HCC). AFB1 is a very potent hepatotoxic and carcinogenic mycotoxin which is frequently reported as a food contaminant. Epigenetic modifications provoked by environmental exposures, such as AFB1, may create a so called persistent "epigenetic memory" or "footprint". Deregulation of epigenetic mechanisms has actually been reported in HCC patients following AFB1 exposure; however no attempts have yet been made to investigate early effects on the epigenome level which may be persistent on longer term thereby possibly initiating carcinogenic events. In this study, we aim to identify methyl DNA-mRNA-interactions representative for a persistent epigenetic "footprint" associated with the early onset of AFB1-induced HCC. For this, primary human hepatocytes were exposed to 0.3 M of AFB1 for 5 days. Persistent epigenetic effects were m easured 3 days after terminating the carcinogenic treatment. Whole genome DNA methylation changes and whole genome transcriptomic analysis were analyzed applying microarray technologies, and cross-omics interactions were evaluated. Upon combining transcriptomics data with results on DNA methylation, a range of persistent hyper- and hypomethylated genes was identified which appeared also affected on the transcriptome level. For six of the hypomethylated and upregulated genes, namely TXNRD1, PCNA, CCNK, DIAPH3, RAB27A and HIST1H2BF, a clear role in carcinogenic events could be identified. This study is the first to report on a carcinogen-induced persistent impact on the "epigenetic footprint" in relation with the transcriptome which could be indicative for the early onset of AFB1-related development of HCC.
Publication Title
Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma.
Sample Metadata Fields
Specimen part
View Samples