Brominated flame retardants effects on the liver transcriptome
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PROVIDER: PRJNA642151 | ENA |
REPOSITORIES: ENA
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Project description:Organophosphorous flame retardants (PFRs) were first reported in the late 1970, and today they account for approximately 20 % of the total use of flame retardants in Europe. PFRs are found ubiquitously in the environment, including remote areas stretching from the Arctic to the Antarctic. Generally, similar levels of PFRs is observed between Arctic and more rural areas. The toxicity of PFRs varies depending on their chemical structure. The World Health Organization have reported LC50 values for mammals and aquatic organisms with high variation from 4.2 to 180 mg/L or 707 to 4700 mg/kg body weight, depending on substance and test species. However, little is known about the toxicity and physiological effects of PFRs to fish, particularly in the Arctic species. Hence, the objective of this study is to determine the effects of PFR exposure on hepatic gene expression patterns in Atlantic cod (Gadus morhua) using liver explants in vitro. Liver explants were exposed to 2-Ethylhexyl diphenyl phosphate (EHDPP), tris(2-chloroisopropyl)phosphate (TCPP), and a mixture of both EHDPP and TCPP for 0, 24 and 48 hours. Samples were analyzed for gene expresson profiling using RNAseq. RNAsequening results suggest that exposure to PFRs differentially expressed genes involved in xenobiotic metabolism. We did not observe any chemical-specific effects on gene expression patterns. However, temporal changes in gene expression were observed. Most of the differentially expressed genes (DE) in 24h exposed samples are related in xenobiotic metabolism, whereas in 48h samples DE genes belong to diverse physiological processes.
2017-12-31 | GSE103954 | GEO
Project description:Effects of organophosphate flame retardants on Atlantic cod liver cells
| PRJNA407769 | ENA
Project description:The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity of seven FR chemicals and formulations was assessed on the freshwater crustacean Daphnia magna. Acute 48-h nominal LC50 values for penta- and octabromodiphenyl ether (pentaBDE, octaBDE), Firemaster 550 (FM550), Firemaster BZ-54 (BZ54), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), triphenyl phosphate (TPhP), and nonbrominated BEH-TEBP analog bis(2-ethylhexyl) phthalate (BEHP) ranged from 0.058 mg/L (pentaBDE) to 3.96 mg/L (octaBDE). mRNA expression, (1)H NMR-based metabolomic and lipidomic profiling at 1/10 LC50 revealed distinct patterns of molecular response for each exposure, suggesting pentaPBDE affects transcription and translation, octaBDE and BEH-TEBP affect glycosphingolipid biosynthesis and BZ54 affects Wnt and Hedgehog signal pathways as well as glycosaminoglycan degradation. Brominated components of FM550 (i.e., BZ54) were significantly higher in Daphnia after 48 h following 1/10 LC50 exposure. FM550 elicited significant mRNA changes at five concentrations across a range from 1/10^6 LC50 to 1/2 LC50. Analyses suggest FM550 impairs nutrient utilization or uptake in Daphnia. Seven flame retardant formulations and equal volume solvent (DMSO) controls for each; four exposed and three or four biological replicates per condition.
2015-11-06 | E-GEOD-74736 | biostudies-arrayexpress
Project description:Human HepG2/C3A cells were exposed to indoor dust reference material SRM2585; DMBA (dimethylbenzanthracene); HBCD (hexabromocyclododecane); two different mixtures of flame retardants (all dissolved in 0.1% DMSO) or 0.1% DMSO alone for 72h. RNA was prepared and labeled with Cy3 then hybridized to Agilent SurePrint G3 Human GE v2 8x60k Microarrays, Agilent design ID 039494.
2015-10-01 | E-MTAB-3324 | biostudies-arrayexpress
Project description:RNA-seq provided a general overview of the gene expression profiles of the digestive glands of Mactra veneriformis exposed to 2, 2′,4,4′-tetrabromodiphenyl ether (BDE-47, a type of widely used brominated flame retardants).
2019-10-19 | GSE88918 | GEO
Project description:Tris(2-chloroethyl) phosphate (TCEP) is a pervasive flame retardant that has been identified as a chemical of concern given its health effects and therefore its use has since been tightly regulated. Tris(2-chloroisopropyl) phosphate (TCIPP), an analogue of TCEP, is believed to be its replacement. However, compared to TCEP, little is known of the toxicological impacts of TCIPP. We used RNA sequencing as unbiased and sensitive tool to identify and compare effects on a transcriptome level of TCEP and TCIPP in the human hepatocellular carcinoma cell line, HepG2. We identified that compared to other flame retardants, TCEP and TCIPP had little cytotoxicity. Treatment with sub-cytotoxic concentrations of the two compounds revealed that both chemicals elicited similar effects; both compounds were found to affect genes involved in immune responses and steroid hormone biosynthesis, while also affecting xenobiotic metabolism pathways in a similar manner. Specifically for effects on immune responses, both compounds were shown to alter the expression of the receptor of the potent and pleiotropic complement component, C5a. Additionally, expression of genes encoding for effector proteins involved in the complement cascade along with other potent inflammatory regulators were found altered in response to TCEP and TCIPP, further emphasizing their potential effects on immune function. Taken together, given that TCIPP elicited similar effects compared to TCEP, and at lower concentrations, the potential health effects of TCIPP need to be further studied for a complete risk assessment of the compound.
2018-01-20 | GSE109463 | GEO
Project description:The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity of seven FR chemicals and formulations was assessed on the freshwater crustacean Daphnia magna. Acute 48-h nominal LC50 values for penta- and octabromodiphenyl ether (pentaBDE, octaBDE), Firemaster 550 (FM550), Firemaster BZ-54 (BZ54), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), triphenyl phosphate (TPhP), and nonbrominated BEH-TEBP analog bis(2-ethylhexyl) phthalate (BEHP) ranged from 0.058 mg/L (pentaBDE) to 3.96 mg/L (octaBDE). mRNA expression, (1)H NMR-based metabolomic and lipidomic profiling at 1/10 LC50 revealed distinct patterns of molecular response for each exposure, suggesting pentaPBDE affects transcription and translation, octaBDE and BEH-TEBP affect glycosphingolipid biosynthesis and BZ54 affects Wnt and Hedgehog signal pathways as well as glycosaminoglycan degradation. Brominated components of FM550 (i.e., BZ54) were significantly higher in Daphnia after 48 h following 1/10 LC50 exposure. FM550 elicited significant mRNA changes at five concentrations across a range from 1/10^6 LC50 to 1/2 LC50. Analyses suggest FM550 impairs nutrient utilization or uptake in Daphnia.
2015-11-06 | GSE74736 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-07-15 | GSE153366 | GEO
Project description:Polychlorinated diphenyl ethers are lipophilic, persistent, and bioaccumulable compounds widely used as flame-retardants. These are chemicals of increasing environmental concern due to their lipophilic, persistent, and bioaccumulable characteristics. The objective of this study was to analyze the potential bioavailability and bioaccumulation of BDE-209 as a source of toxicity. Zebrafish embryos were exposed for 8 days to sediments spiked with an environmentally relevant concentration of BDE-209. We analyzed gene expression changes, thyroid function, and several markers for neurotoxicity. Results of this research highlight the need to consider the capability of BDE-209 to be bioavailable and bioaccumulate, indicating the potential hazardous effects.
2013-01-01 | GSE39169 | GEO
Project description:There is a growing need to understand the potential neurotoxicity of organophosphate ester flame retardants (OPFRs) and plasticizers because use and, consequently, human exposure, is rapidly expanding. We have previously shown in rats that developmental exposure to the commercial FR mixture Firemaster® 550 (FM 550), which contains OPFRs, results in sex-specific behavioral effects, and identified the placenta as a potential target of toxicity. The placenta is a critical coordinator of fetal growth and neurodevelopment, and a source of neurotransmitters (NTs) for the developing brain. We have shown in rats and humans that FRs accumulate in placental tissue, and induce functional changes, including altered neurotransmitter (NT) production. Here we sought to establish if OPFRs (triphenyl phosphate, TPHP, and a mixture of isopropylated triarylphosphate isomers, ITPs) alter placental function and fetal forebrain development, with disruption of tryptophan (Trp) metabolism as a primary pathway of interest. Wistar rat dams were orally exposed to OPFRs (0, 500, 1,000, or 2,000 μg/day) or a serotonin (5-HT) agonist (5-MT) for 14 days during gestation and placenta and fetal forebrain tissues collected for analysis by transcriptomics and metabolomics. Relative abundance of genes responsible for the transport and synthesis of placental 5-HT were disrupted, and multiple neuroactive metabolites in the 5-HT and kynurenine (Kyn) metabolic pathways were upregulated. Additionally, 5-HTergic projections were significantly longer in the fetal forebrains of exposed males. These findings suggest that OPFRs have the potential to impact the 5-HTergic system in the fetal forebrain by disrupting placental Trp metabolism.
2020-04-08 | GSE148266 | GEO