Nanotoxicogenomic study of ZnO and TiO2 responses
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Soile Tuomela
PROVIDER: E-GEOD-39444 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:A comprehensive in vitro assessment of two commercial metal oxide nanoparticles, TiO2 and ZnO, was performed using human monocyte-derived macrophages (HMDM), monocyte-derived dendritic cells (MDDC), and T cell leukemia-derived cell line (Jurkat). TiO2 nanoparticles were found to be non-toxic whereas ZnO nanoparticles caused dose-dependent cell death. Subsequently, global gene expression profiling was performed to identify signaling pathways underlying the cytotoxicity caused by ZnO nanoparticles. Analysis was done with doses, 1ug/ml and 10ug/ml after 6 and 24 hours of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10ug/ml ZnO nanoparticles, while in MDDCs only 12 genes were affected. In Jurkat cells, 980 genes were differentially expressed. It is noteworthy that the gene expression of metallothioneins was upregulated in all the three cell types. In addition to the common ZnO-inducible changes, a notable proportion of the genes were regulated in a cell type-specific manner. Using a panel of ZnO nanoparticles, we obtained an additional support that the cellular response to ZnO nanoparticles is caused by particle dissolution. Gene ontology analysis revealed that the top biological processes disturbed in HMDM and Jurkat cells were regulating cell death and growth. In addition, genes controlling immune system development were affected. Bioinformatics assessment showed that the top human disease category associated with ZnO-responsive genes in both HMDM and Jurkat cells was cancer. Overall, the study revealed novel genes and pathways for mediating ZnO nanoparticle-induced toxicity and demonstrated the value of assessing nanoparticle responses through combined transcriptomics and bioinformatics approach. Nanoparticles used in the study: ZnO-1 commercial (IBU-tec advanced materials AG), ZnO-2 (mandelic acid coated ZnO-1), ZnO-3 (mercaptopropyl-trimethoxysilane coated ZnO-1), ZnO-4 (methoxyl coated ZnO), ZnO-5 (diethylene glycol modified ZnO) and ZnO-9 (folic acid modified ZnO). Detailed particle production and characterization data can be found from the articles: Buerki-Thurnherr et al. 2012 Nanotoxicology and Tuomela et al. Altogether 71 samples were analyzed: 3 biological replicates of HMDM samples (untreated control, 10ug/ml of ZnO-1, 6 and 24 hours), 3 biological replicates of MDDC samples (untreated control, 6 and 24 hours), 7 biological replicates of MDDC samples (10ug/ml of ZnO-1, 24 hours), 3 replicates of Jurkat cells (untreated control, 10ug/ml of ZnO-1, 6 and 24 hours), 3 replicates of Jurkat cells (untreated control, 10ug/ml of ZnO-2, ZnO-3, ZnO-5 or ZnO-9, or 10, 25, 50 or 100ug/ml of ZnO-4, 24 hours).
2013-07-25 | E-GEOD-39330 | biostudies-arrayexpress
Project description:A comprehensive in vitro assessment of two commercial metal oxide nanoparticles, TiO2 and ZnO, was performed using human monocyte-derived macrophages (HMDM), monocyte-derived dendritic cells (MDDC), and T cell leukemia-derived cell line (Jurkat). TiO2 nanoparticles were found to be non-toxic whereas ZnO nanoparticles caused dose-dependent cell death. Subsequently, global gene expression profiling was performed to identify signaling pathways underlying the cytotoxicity caused by ZnO nanoparticles. Analysis was done with doses, 1M-BM-5g/ml and 10M-BM-5g/ml after 6 and 24 hours of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10M-BM-5g/ml ZnO nanoparticles, while in MDDCs only 12 genes were affected. In Jurkat cells, 980 genes were differentially expressed. It is noteworthy that the gene expression of metallothioneins was upregulated in all the three cell types. In addition to the common ZnO-inducible changes, a notable proportion of the genes were regulated in a cell type-specific manner. Using a panel of ZnO nanoparticles, we obtained an additional support that the cellular response to ZnO nanoparticles is caused by particle dissolution. Gene ontology analysis revealed that the top biological processes disturbed in HMDM and Jurkat cells were regulating cell death and growth. In addition, genes controlling immune system development were affected. Bioinformatics assessment showed that the top human disease category associated with ZnO-responsive genes in both HMDM and Jurkat cells was cancer. Overall, the study revealed novel genes and pathways for mediating ZnO nanoparticle-induced toxicity and demonstrated the value of assessing nanoparticle responses through combined transcriptomics and bioinformatics approach. Altogether 90 samples were analyzed originating from three biological replicates of HMDM, MDDC or Jurkat cells containg untreated control cells, ZnO or TiO2 treated cells with doses 1M-BM-5g/ml and 10M-BM-5g/ml. The sample timepoints were 6 hours and 24 hours.
2013-07-25 | E-GEOD-39316 | biostudies-arrayexpress
Project description:The aim of this experiment was to compare the gene expression in MoDCs differentiating for 2 days in the presence or absence of LPS.
2012-01-01 | E-MTAB-658 | biostudies-arrayexpress
Project description:The transcriptomic changes induced in the human liver cell line HepG2 by Azathriopine (250M-BM-5M, Sigma-Aldrich), Furan (2mM, Sigma-Aldrich), Tetradecanoyl phorbol acetate (500nM, Sigma-Aldrich), Tetrachloroethylene (2mM, Sigma-Aldrich), Diazinon (250M-BM-5M, Sigma-Aldrich) and Dmannitol (250M-BM-5M, Sigma-Aldrich) during 4, 8, 24, 48 and 72hrs As a solvent control for Azathriopine, Furan, Diazinon and Tetradecanoyl phorbol acetate, DMSO was used (0.5%); As a solvent control for tetrachloroethylene, ethanol was used (0.5%); As a solvent control for D-mannitol, HBSS was used (0.5%) The study investigated differential gene expression in HepG2 cell line mRNA following 4, 8, 24, 48 and 72h hours of exposure to Azathriopine, Furan, Tetradecanoyl phorbol acetate, Tetrachloroethylene, Diazinon, D-mannitol, DMSO solvent control, ethanol solvent control and HBSS solvent control. Three biological replicates per compound/solvent. In total 135 arrays were analyzed in total.
2015-01-13 | E-GEOD-58235 | biostudies-arrayexpress
Project description:The transcriptomic changes induced in the human liver cell line HepG2 by 100M-BM-5M menadione, 200M-BM-5M TBH or 50M-BM-5M H2O2 after treatment for 0.5, 1, 2, 4, 6, 8 and 24h. The study investigated differential gene expression in HepG2 cell line mRNA following 0.5, 1, 2, 4, 6, 8 and 24h hours of exposure to 100M-BM-5M menadione, 200M-BM-5M TBH or 50M-BM-5M H2O2 and medium without compound. Three biological replicates per compound/solvent. In total 126 arrays.
2013-05-31 | E-GEOD-39291 | biostudies-arrayexpress
Project description:In this study, we reprogrammed fibroblasts from two azoospermic Klinefelter syndrome (KS) patients, and two healthy male and one healthy female donor with an efficient integration-free method using episomal plasmids and laminin-521 (LN521). Whole genome transcriptomics analysis showed differentially expressed genes between KS and healthy male donors with enrichment in gene ontology (GO) terms associated with fertility, cardiovascular development, ossification and brain development, for both KS hiPSCs and fibroblasts, correlating with the KS clinical phenotype. Thorough XCI analysis combining transcriptomics data, RNA FISH and H3K27me3 staining, revealed skewed XCI in one KS fibroblast line and variability in XCI state of KS hiPSCs similar to female hiPSCs, showing either XaXi or XaXe status. Furthermore, we found up-regulated X-linked genes involved in nervous system development, synaptic transmission as well as metabolic processes supporting the potential use of KS derived hiPSC as an in vitro model for KS.
2019-10-05 | E-MTAB-7340 | biostudies-arrayexpress
Project description:The endocrine disrupting chemical bisphenol A (BPA) can affect reproductive organs, tissues and cells in several species. Treatment of human endometrial endothelial cells (HEECs) with 50 µM BPA decreased their proliferation compared with the control. Microarray analyses revealed that BPA affected biological processes such as the cell cycle, cell division, and cytoskeleton organization, confirming the results of the proliferation assay. Expression of three of the most differentially expressed genes identified in the microarray analysis was verified by real-time quantitative reverse transcription polymerase chain reaction in five HEEC cultures obtained from women in the proliferative phase and in five cultures obtained from women in the secretory phase of the menstrual cycle after treatment with BPA. The present study supports our previous findings of decreased proliferation and increased cell death in response to BPA, and may offer important clues to the mechanisms of action of BPA. Keywords: Exposure analysis Two-condition experiments, BPA-exposed vs. control HEEC. Biological replicates: 5 HEEC cultures, independently grown, exposed and harvested. One replicate per array. Dye-swaps for exposed and reference samples between replicates.
2010-05-25 | E-GEOD-10802 | biostudies-arrayexpress
Project description:The endocrine disrupting chemical o,p'-DDT can affect reproductive organs, tissues and cells in several species. Treatment of human endometrial endothelial cells (HEEC) with 50 µM o,p'-DDT decreased the cell proliferation compared to the control. Microarray analyses revealed that o,p'-DDT affected biological processes such as the cell cycle, cell division, defence response and lipid and steroid metabolism, in cellular components such as the plasma membrane and chromosomes, with molecular functions involved in signalling, receptor and cytokine activity, confirming the results of the proliferation assay. The present study supports our previous findings of decreased proliferation and increased cell death in response to o,p'-DDT, and may offer important clues in the deduction of the mechanisms of action of o,p'-DDT. Keywords: Exposure analysis Two-condition experiments, o,p'-DDT-exposed vs. control HEEC, and individual control vs control pool. Biological replicates: 5 HEEC cultures, independently grown, exposed and harvested. One replicate per array. Dye-swaps for exposed and reference samples between replicates. variable = Exposure: o,p'-DDT-treated: Indiv1 s1 op-DDT Cy3, Indiv2 s19 op-DDT Cy3, Indiv3 s37 op-DDT Cy3, Indiv4 s55 op-DDT Cy5, Indiv5 s73 op-DDT Cy5 variable = Exposure: control: Indiv1 s2 control Cy5, Indiv2 s20 control Cy5, Indiv3 s38 control Cy5, Indiv4 s56 control Cy3, Indiv5 s74 control Cy3 variable = Exposure: individual control: Indiv1 s17 control Cy3, Indiv2 s35 control Cy5, Indiv3 s53 control Cy3, Indiv4 s71 control Cy5, Indiv5 s89 control Cy3 variable = Exposure: control pool: Pooled control s18/36/54/72/90 Cy5, Pooled control s18/36/54/72/90 Cy3, Pooled control s18/36/54/72/90 Cy5, Pooled control s18/36/54/72/90 Cy3, Pooled control s18/36/54/72/90 Cy5 repeat = Biological replicate: Indiv1 s1 op-DDT Cy3, Indiv1 s2 control Cy5, Indiv1 s17 control Cy3, sample 18 in Pooled control repeat = Biological replicate: Indiv2 s19 op-DDT Cy3, Indiv2 s20 control Cy5, Indiv2 s35 control Cy5, sample 36 in Pooled control repeat = Biological replicate: Indiv3 s37 op-DDT Cy3, Indiv3 s38 control Cy5, Indiv3 s53 control Cy3, sample 54 in Pooled control repeat = Biological replicate: Indiv4 s55 op-DDT Cy5, Indiv4 s56 control Cy3, Indiv4 s71 control Cy5, sample 72 in Pooled control repeat = Biological replicate: Indiv5 s73 op-DDT Cy5, Indiv5 s74 control Cy3, Indiv5 s89 control Cy3, sample 90 in Pooled control
2007-10-10 | E-GEOD-9252 | biostudies-arrayexpress
Project description:objection: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases Method: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment Between April 2007 and June 2009, 31 patients with active RA, PsA and Ps who were naïve to anti-TNF agents, were recruited from the Faculty Rheumatology Clinics at the University of Rochester Medical Center after informed, written consent was obtained in a protocol approved by the Research Subjects Review Board at the University of Rochester Medical Center. Of the 31 subjects, 9 had active RA and 12 had PsA despite treatment with Disease Modifying Anti-Rheumatic Drugs (DMARDs). Also, 10 patients with extensive Ps (>5% BSA) documented by a dermatologist, were enrolled and they were examined by a rheumatologist to exclude the presence of inflammatory arthritis. Nineteen healthy controls were also recruited.
2014-10-29 | E-GEOD-57383 | biostudies-arrayexpress
Project description:Splenic Transitional Type-1 B-cells from CBA wild-type mice, X-linked immunodeficiency mice and Bruton's tyrosine kinase knock-out mice. Two replicates where run on Affymetrix 420 2.0 arrays for CBA wild-type, Xid samples and the Btk KO samples. Bruton's tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase important for B-lymphocyte maturation. Mutations in Btk give rise to the primary immunodeficiency disease X-linked agammaglobulinemia (XLA) in man and X-linked immunodeficiency (Xid) in mice. Recent studies have subdivided the mouse immature, or transitional, B-cells into two distinct subsets according to their respective surface markers. Transitional type 1 (T1) and transitional type 2 (T2) cells are also located in distinct anatomic locations. Based on a limited number of markers it has previously been reported that the earliest phenotypic sign of Btk deficiency is manifested at the T2 stage in mice. Here, we report on distinct genome-wide transcriptomic signature differences found in T1 B-lymphocytes from Btk-defective compared to normal mice and demonstrate that Btk deficiency is visible already at this stage. 2 replicates of T1 B-cells from CBA (WT), Xid samples and the Btk KO samples
2014-01-10 | E-GEOD-53946 | biostudies-arrayexpress