PFOS effects on MCF-10A
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ABSTRACT:
PROVIDER: PRJEB74485 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Recently it was discovered that the perfluorooctane sulfonate (PFOS) detected in wildlife, such as fish-eating birds, had a greater proportion of linear PFOS (L-PFOS) than the manufactured technical product (T-PFOS), which contains linear and branched isomers. This suggests toxicological studies based on T-PFOS data may inaccurately assess exposure risk to wildlife. To determine if PFOS effects were influenced by isomer content we compared the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either L-PFOS or T-PFOS using Agilent microarrays. At equal concentrations (10 μM), T-PFOS altered the expression of more transcripts (340, >1.5 fold change, p<0.05) compared to L-PFOS (130 transcripts). Higher concentrations of L-PFOS (40 μM) were also less transcriptionally disruptive (217 transcripts) than T-PFOS at 10 μM. Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, hepatic system development and cellular growth and proliferation. Pathway and interactome analysis suggested that genes may be affected through the RXR receptor, oxidative stress response, TP53 signaling, MYC signaling, Wnt/β-catenin signaling and PPARγ and SREBP receptors. In all functional categories and pathways examined, the response elicited by T-PFOS was greater than L-PFOS. These data show that T-PFOS elicits a greater transcriptional response in CEH than L-PFOS alone and demonstrates the importance of considering the isomer-specific toxicological properties of PFOS when assessing exposure risk. Reference Design. Reference = pool of equal parts of all control and treated samples. Control groups and 5 treatment groups. Control samples were CEH exposed DMSO only (vehicle solvent). Treatments were: CEH exposed to 10 uM L-PFOS, 40 uM L-PFOS, 10 uM T-PFOS, 0.03 nM TCDD and 1 nM TCDD.
2011-10-28 | E-GEOD-33291 | biostudies-arrayexpress
Project description:PFOS, a member of the chemical group known as per- and polyfluoroalkyl substances (PFAS), is a well-documented environmental contaminant. Its high bioaccumulation potential and long elimination half-life can disrupt multiple biological pathways negatively affecting human health. The gastrointestinal tract (GI) is directly exposed to environmental pollutants via contaminated drinking water and food, potentially influencing intestinal homeostasis under both physiological and pathological conditions. Although some studies have highlighted the potential role of PFOS in tumor development, scientific literature on PFOS exposure in the GI is limited and the association between this environmental pollutant and GI-associated diseases remains to be determined. Therefore, this study aims to delineate the effects of PFOS on normal intestinal cells. The effect of PFOS on gene expression profiles was assessed through RNAseq analysis conducted on the intestinal tissue of C57BL/6 mice. Through RNAseq analysis, we identified the top pathways upregulated by PFOS as cancer, lipid metabolism and immune system. The KEGG analysis further highlighted significant gene enrichment in pro-oncogenic signaling pathways, including NOTCH, WNT/β-catenin and TGF-β. The RNAseq, q-RT-PCR and western blot analyses of normal intestinal tissues revealed that PFOS exposure leads to downregulation of 3-hydroxy-3-methylglutaryl-Coa synthase 2 (HMGCS2), a key enzyme in the synthesis of β-hydroxybutyrate (βHB), a critical ketogenic molecule. In summary, our data suggests that PFOS may induce GI pathological changes that can increase the risk of CRC development. We identified that downregulation of ketogenesis and upregulation of lipid metabolism are the major effects of PFOS exposure in intestinal epithelium.
2024-06-12 | GSE248402 | GEO
Project description:This series was used for two studies: Study 1: Recently it was discovered that the perfluorooctane sulfonate (PFOS) detected in wildlife, such as fish-eating birds, had a greater proportion of linear PFOS (L-PFOS) than the manufactured technical product (T-PFOS), which contains linear and branched isomers. This suggests toxicological studies based on T-PFOS data may inaccurately assess exposure risk to wildlife. To determine if PFOS effects were influenced by isomer content we compared the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either L-PFOS or T-PFOS using Agilent microarrays. At equal concentrations (10 ?M), T-PFOS altered the expression of more transcripts (340, >1.5 fold change, p<0.05) compared to L-PFOS (130 transcripts). Higher concentrations of L-PFOS (40 ?M) were also less transcriptionally disruptive (217 transcripts) than T-PFOS at 10 ?M. Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, hepatic system development and cellular growth and proliferation. Pathway and interactome analysis suggested that genes may be affected through the RXR receptor, oxidative stress response, TP53 signaling, MYC signaling, Wnt/?-catenin signaling and PPAR? and SREBP receptors. In all functional categories and pathways examined, the response elicited by T-PFOS was greater than L-PFOS. These data show that T-PFOS elicits a greater transcriptional response in CEH than L-PFOS alone and demonstrates the importance of considering the isomer-specific toxicological properties of PFOS when assessing exposure risk. Study 2: In many bird populations, concentrations of perfluoroundanoic acid (PFUdA) are second only to perfluorooctane sulfonate (PFOS) among perfluoroalkyl compounds. Here, we used microarrays to characterize the transcriptional response of cultured chicken embryonic hepatocytes (CEH) to PFUdA and compared it to the response induced by PFOS. At non-cytotoxic doses, PFUdA (1 or 10 ?M) disrupted the expression of more genes (854) than PFOS (447, at 10 or 40 ?M) in CEH. Using functional, pathway and interactome analysis we identified several potentially important modes-of-action (MoAs) for PFUdA and some associated key events, including the suppression of the acute-phase response (APR) through peroxisome proliferator activated receptor activation. We then measured the expression of five APR genes, fibrinogen alpha (fga), fibrinogen gamma (fgg), thrombin (f2), plasminogen (plg), and protein C (proC), in the liver of chicken embryos exposed in ovo to PFUdA. The expression of fga, f2, and proC were down-regulated in embryo livers (100 or 1000 ng/g, p<0.1) as predicted from microarray analysis, whereas fibrinogen gamma (fgg) was up-regulated and plg was not significantly affected. Our results demonstrate PFUdA is more transcriptionally disruptive than PFOS in CEH. Additionally, we identified APR suppression as a potentially important and environmentally relevant MoA. These findings suggest in ovo exposure of birds to PFUdA could lead to post-hatch developmental deficiencies, such as impaired immune response.
2011-10-29 | GSE33291 | GEO
Project description:Perfluorooctanesulfonic acid (PFOS) is a persistent, bio-accumulative pollutant that has been used for the last 60+ years in numerous industrial and commercial applications. In mice, PFOS administration is known to induce hepatomegaly and hepatic steatosis. The aim of the present study was to evaluate potential PFOS and diet interactions and explore the mechanism of PFOS induced liver lipid accumulation. Prior to PFOS administration, mice were fed either a standard chow diet (SD) or 60% kCal high fat diet (HFD) for 4 weeks to establish significant body weight increase. After 4 weeks of diet acclimation, the treatment groups received 0.0003% PFOS in diet for an additional 10 weeks. In addition, a subset of the mice fed HFD were switched to a SD (H-SD) to mimic weight-loss induced improvement of hepatic steatosis. A total of six treatment groups: i) SD, ii) HSD, iii) HFD (H), iv) SD +PFOS(SDP), v) H-SD +PFOS (HSDP), and vi) HFD +PFOS (HP) were included. PFOS and lipid concentrations were measured in both serum and liver. Relative liver mRNA expression was determined by targeted bead array and proteins were quantified using untargeted mass spectrometry. PFOS exposure increased liver weight, and in the HFD increased liver triglycerides and liver cholesterol content. Gene and protein expression in the liver demonstrated that PFOS exposure induced lipid utilization and xenobiotic metabolism pathways, and in a HFD, induced lipid synthesis. The data suggests that PFOS exposure acts on lipid utilization genes and exacerbates hepatic steatosis in mice fed a HFD.
2020-09-30 | PXD016161 | Pride
Project description:A comparison of different energetics based techniques for the characterization of two mammalian breast cell lines, MCF-7 a luminal A breast cancer cell line and MCF-10A a normal human breast cell line. The techniques of stability of proteins from rates of oxidation (SPROX), thermal proteome profiling (TPP), and conventional expression level analyses were compared and the relative advantages and disadvantages are discussed.
2023-02-22 | PXD036268 | Pride
Project description:Exposure to per- and polyfluoroalkyl substances (PFASs) such as perfluorooctanesulfonic acid (PFOS) has been associated with congenital heart disease (CHD) and decreased birth weight. PFAS exposure can disrupt signaling pathways relevant for cardiac development in stem cell derived cardiomyocyte assays, including PFOS-induced disruption to in vitro cardiac differentiation into contracting spheroids of cardiomyocytes; the PluriBeat assay. Notably, cell line origin can affect how the assay respond to PFAS exposure. Herein, we examine the effect of PFOS on cardiomyocyte differentiation by transcriptomics profiling of two different human induced pluripotent stem cell (hiPSC) lines, to see if they exhibit a common pattern of disruption. Two stages of differentiation, the cardiac progenitor stage (early) and the cardiomyocyte stage (late), were investigated.
2022-05-03 | GSE202077 | GEO
Project description:Perfluorooctanesulfonic acid (PFOS) is a persistent anthropogenic chemical that can affect the thyroid hormone system in humans. In experimental animals, PFOS exposure decreases thyroxine (T4) and triiodothyronine (T3) levels, without a compensatory upregulation of thyroid stimulating hormone (TSH). In adults, THs are regulated by the hypothalamus-pituitary-thyroid (HPT) axis, but also organs such as the liver and potentially the gut microbiota. PFOS and other xenobiotics can therefore potentially disrupt the TH system through various entry points of disruption. To start addressing this issue, we performed a PFOS exposure study to identify effects in multiple organs and pathways simultaneously.
2022-05-04 | GSE196133 | GEO
Project description:Perfluorooctanesulfonate (PFOS) has been widely used in a variety of industrial and commercial applications as a surfactant and stain repellent. PFOS causes liver damage (including liver tumors) in experimental animals, primarily via interaction with PPARa and CAR/PXR. We investigated the involvement of microRNAs (miRNAs) in PFOS-induced hepatotoxicity, and mechanisms involved in abnormal TH homeostasis, in the livers of adult male rats exposed in feed to 50 mg PFOS/kg diet for 28 days. PFOS-treated rats exhibited expected histopathological and clinical chemistry changes. Global gene expression changes were consistent with the involvement of PPARα and CAR/PXR in PFOS-induced effects. Thirty-eight miRNAs were significantly altered. Three members of the miR-200 family were the most increased, while miR-122 and miR-21 were the most decreased, in PFOS-treated relative to control rats. Expression of the miR-23b/27b/24 cluster also decreased in PFOS-treated animals. Pathway analysis of miRNAs and associated gene expression changes demonstrated enrichment of transcripts involved in epithelial to mesenchymal transition (EMT), which is a primary process involved in tumor cell motility and cancer metastasis. Liver expression analysis revealed transcripts that may mediate PFOS effects on thyroid hormone (TH) homeostasis including: activation of the CAR/PXR pathway, phase II/III enzymes, and deiodinase. These changes are consistent with low serum TH due to enhanced metabolic clearance of TH. However, most TH hepatic target genes were not altered in a manner consistent with reduced TH signalling; suggesting that PFOS exposure did not induce functional hypothyroidism. Collectively, PFOS-induced miRNA perturbations were strongly associated with EMT suggesting an important role for miRNAs in PFOS-induced hepatotoxicity. The work also provides novel insights into the effects of PFOS on TH homeostasis.
2015-08-01 | GSE69520 | GEO
Project description:Perfluorooctanesulfonate (PFOS) has been widely used in a variety of industrial and commercial applications as a surfactant and stain repellent. PFOS causes liver damage (including liver tumors) in experimental animals, primarily via interaction with PPARa and CAR/PXR. We investigated the involvement of microRNAs (miRNAs) in PFOS-induced hepatotoxicity, and mechanisms involved in abnormal TH homeostasis, in the livers of adult male rats exposed in feed to 50 mg PFOS/kg diet for 28 days. PFOS-treated rats exhibited expected histopathological and clinical chemistry changes. Global gene expression changes were consistent with the involvement of PPARα and CAR/PXR in PFOS-induced effects. Thirty-eight miRNAs were significantly altered. Three members of the miR-200 family were the most increased, while miR-122 and miR-21 were the most decreased, in PFOS-treated relative to control rats. Expression of the miR-23b/27b/24 cluster also decreased in PFOS-treated animals. Pathway analysis of miRNAs and associated gene expression changes demonstrated enrichment of transcripts involved in epithelial to mesenchymal transition (EMT), which is a primary process involved in tumor cell motility and cancer metastasis. Liver expression analysis revealed transcripts that may mediate PFOS effects on thyroid hormone (TH) homeostasis including: activation of the CAR/PXR pathway, phase II/III enzymes, and deiodinase. These changes are consistent with low serum TH due to enhanced metabolic clearance of TH. However, most TH hepatic target genes were not altered in a manner consistent with reduced TH signalling; suggesting that PFOS exposure did not induce functional hypothyroidism. Collectively, PFOS-induced miRNA perturbations were strongly associated with EMT suggesting an important role for miRNAs in PFOS-induced hepatotoxicity. The work also provides novel insights into the effects of PFOS on TH homeostasis.
2015-08-01 | GSE69521 | GEO
Project description:Perfluorooctanesulfonate (PFOS) has been widely used in a variety of industrial and commercial applications as a surfactant and stain repellent. PFOS causes liver damage (including liver tumors) in experimental animals, primarily via interaction with PPARa and CAR/PXR. We investigated the involvement of microRNAs (miRNAs) in PFOS-induced hepatotoxicity, and mechanisms involved in abnormal TH homeostasis, in the livers of adult male rats exposed in feed to 50 mg PFOS/kg diet for 28 days. PFOS-treated rats exhibited expected histopathological and clinical chemistry changes. Global gene expression changes were consistent with the involvement of PPARα and CAR/PXR in PFOS-induced effects. Thirty-eight miRNAs were significantly altered. Three members of the miR-200 family were the most increased, while miR-122 and miR-21 were the most decreased, in PFOS-treated relative to control rats. Expression of the miR-23b/27b/24 cluster also decreased in PFOS-treated animals. Pathway analysis of miRNAs and associated gene expression changes demonstrated enrichment of transcripts involved in epithelial to mesenchymal transition (EMT), which is a primary process involved in tumor cell motility and cancer metastasis. Liver expression analysis revealed transcripts that may mediate PFOS effects on thyroid hormone (TH) homeostasis including: activation of the CAR/PXR pathway, phase II/III enzymes, and deiodinase. These changes are consistent with low serum TH due to enhanced metabolic clearance of TH. However, most TH hepatic target genes were not altered in a manner consistent with reduced TH signalling; suggesting that PFOS exposure did not induce functional hypothyroidism. Collectively, PFOS-induced miRNA perturbations were strongly associated with EMT suggesting an important role for miRNAs in PFOS-induced hepatotoxicity. The work also provides novel insights into the effects of PFOS on TH homeostasis. Four RNA samples from control and four from PFOS treated rats were labelled with Cyanine 5-CTP (Cy5) using Low Input Quick Amp Labelling kits (Agilent Technologies Inc.) following the manufacturer’s instruction. Universal rat reference total RNA (Agilent Technologies Inc.) was labelled with Cyanine 3-CTP (Cy3). Cy5-sample cRNA and Cy3-reference cRNA were hybridized to Agilent G4853A SurePrint G3 Rat GE 8 X 60K microarrays (Agilent Technologies Inc.) at 65°C overnight with Agilent hybridization solution. Slides were washed and scanned on an Agilent G2505B microarray scanner at 5 μm resolution, and the data were acquired with Agilent Feature Extraction software version 10.7.3.1. Microarray data quality was confirmed using Agilent Feature Extraction quality control metrics and in-house metrics (boxplots, cluster analyses, and MA plots to identify poor quality outlier arrays). All samples passed the quality control tests and were used for subsequent analyses.
2015-08-01 | E-GEOD-69520 | biostudies-arrayexpress