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Toxic effects of BDE209 in human embryonic kidney 293 cells (HEK 293)

ABSTRACT: PBDEs are widely used in consumer and household products as flame retardants. Many studies have shown that PBDEs could disrupt thyroid hormone homeostasis and adversely affect brain development. Here, we explored the toxical effects of BDE209 on HEK 293 cells and found that BDE209 may have a role in nucleosome remodeling. Many gene sets involved in cancer are enriched at the BDE209-treated sample. This indicates the carcinogenicity of BDE209. Interestingly, the impacts of BDE209 dissoved in DMSO on gene expression are more pronounced than the simple additive effects of BDE209 and DMSO alone.

ORGANISM(S): Homo sapiens

PROVIDER: GSE56361 | GEO | 2014/04/21

SECONDARY ACCESSION(S): PRJNA243130

REPOSITORIES: GEO

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Toxic effects of BDE209 in human embryonic kidney 293 cells (HEK 293)

Project description:PBDEs are widely used in consumer and household products as flame retardants. Many studies have shown that PBDEs could disrupt thyroid hormone homeostasis and adversely affect brain development. Here, we explored the toxical effects of BDE209 on HEK 293 cells and found that BDE209 may have a role in nucleosome remodeling. Many gene sets involved in cancer are enriched at the BDE209-treated sample. This indicates the carcinogenicity of BDE209. Interestingly, the impacts of BDE209 dissoved in DMSO on gene expression are more pronounced than the simple additive effects of BDE209 and DMSO alone. Gene expression profiles of human embryonic kidney 293 cells (HEK 293) cultured in normal medium, and medium containing BDE209 or DMSO were generated by deep sequencing, using Illumina HighSeq2000, respectively..

2014-04-21 | E-GEOD-56361 | biostudies-arrayexpress

A Mixture Reflecting Polybrominated Diphenyl Ether (PBDE) Profiles Detected in Human Follicular Fluid Significantly Affects Steroidogenesis and Induces Oxidative Stress in a Human Granulosa Cell Line

Project description:Brominated flame retardants (BFRs) are incorporated into consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female fertility. Our goal was to elucidate effects of a mixture reflecting human follicular fluid levels of polybrominated flame retardants (PBDEs), the major class of BFRs, on an immortalized human granulosa cell line, the KGN cell line. We showed that cell viability was altered and oxidative stress was induced, as reflected by increased reactive oxygen species formation, at 20 µM of the PBDE mixture. Transcriptomic analysis revealed that several genes showing an altered expression after the PBDE treatment were involved in oxidative stress signaling pathways. Significant dose-dependent reduction of progesterone and estradiol levels was measured after PBDE treatment; expression of genes involved in steroid hormone metabolism, namely CYP1A1, was significantly affected by PBDEs. Treatment with the PBDE mixture also modified genes encoding for members of the transforming growth factor β superfamily like inhibins and cytokines, including the pro-inflammatory factor, interleukin-6 (IL6). Concentration of IL-6 in KGN cell culture media was consistently increased after treatment with the PBDE mixture. Our results clearly demonstrate that the PBDEs detected in human follicular fluid alter human granulosa cell functions by inducing oxidative stress, disrupting steroidogenesis and triggering an inflammatory response. This strengthens the fact that PBDEs are detrimental to ovarian functions and thus, to women’s reproductive health.

2016-05-25 | GSE77963 | GEO

OH-PBDE-induced gene expression profiling in H295R adrenocortical carcinoma cells

Project description:Polybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in a variety of commercial and household products. They have been detected in the environment and accumulate in mammalian tissues and fluids. PBDE toxicity is thought to be associated with endocrine disruption, developmental neurotoxicity and changes in fetal development. Although humans are exposed to PBDEs, our knowledge of the effects of PBDE metabolites on human cells with respect to health risk is insufficient. Two hydroxylated PBDEs (OH-PBDEs), 2-OH-BDE47 and 2-OH-BDE85, were investigated for their effects on cell viability/proliferation, DNA damage, cell cycle distribution and gene expression profiling in H295R adrenocortical carcinoma cells. We show that the two agents are cytotoxic in a dose-dependent manner only at micromolar concentrations, with 2-OH-BDE85 being more toxic than 2-OH-BDE47. However, no DNA damage was observed for either chemical, suggesting that the biological effects of OH-PBDEs occur primarily via non-genotoxic routes. Furthermore, no evidence of aryl hydrocarbon receptor (AHR)-mediated, dioxin-like toxicity was observed. Instead, we report that a micromolar concentration of OH-PBDEs induces transcriptional changes associated with endoplasmic reticulum stress and the unfolded protein response. We discuss whether OH-PBDE bioaccumulation could result in impairment of the adrenocortical secretory function.

2008-12-25 | GSE8588 | GEO

Transcriptomic responses of human hepatocellular carcinoma cells (HepG2/C3A) to dust, flame retardants and dimethylbenzanthracene

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

Gene transcription, metabolite and lipid profiling in eco-indicator daphnia magna indicate diverse mechanisms of toxicity by legacy and emerging flame-retardants.

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

Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via bulk RNA-sequencing

Project description:Similar to the scRNA-Seq data (GSE125272), a surgical menopausal (ovariectomized) mouse model was used to assess how mammary gland tissue was affected by both 17β-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). The PBDE treatments include three analyzed flame retardants: BDE-47, BDE-100 and BDE-153. Bulk RNA-Seq data was created with treatment conditions lasting 1 week. Gene expression changes for PBDE treatment are relatively small compared to E2 treatment. However, along with other studies and experiments, this data is meant to contribute to greater understanding of the interaction of PBDE exposure and estrogen signaling.

2023-03-24 | GSE227872 | GEO

Microarray analysis of gene response to contaminant accumulation in wild largescale suckers

Project description:Toxic compounds such as organochlorine pesticides (OCs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ether flame retardants (PBDEs) have been detected in fish, birds, and aquatic mammals that live in the Columbia River or use the river as a food source. We developed a custom microarray for largescale suckers (Catostomus macrocheilus) and used it to investigate the molecular effects of contaminant exposure on wild fish in the Columbia River. Using Significance Analysis of Microarrays (SAM) we identified 72 probes representing 69 unique genes with expression patterns that correlated with hepatic tissue levels of OCs, PCBs, or PBDEs. These genes were involved in many biological processes previously shown to respond to contaminant exposure, including drug and lipid metabolism, apoptosis, cellular transport, oxidative stress, and cellular chaperone function. The relation between gene expression and contaminant burden suggests that these genes may respond to environmental contaminant exposure and are promising candidates for further field and laboratory studies to develop biomarkers for monitoring exposure of wild fish to contaminant mixtures found in the Columbia River Basin Correlation between contaminant exposure and gene expression profiles of wild largescale suckers collected from three different sites in the Columbia River. At each site, liver samples of six to eight different fish were analyzed using microarrays.

2013-12-04 | E-GEOD-41016 | biostudies-arrayexpress

Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

Project description:Exposure to estrogen and its mimics during menopausal transition is thought to modify the structure of mammary gland. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary gland tissue was affected by both 17β-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). Three analyzed flame retardants, BDE-47, BDE-100 and BDE-153, are most frequently detected in human serum from all over the world. During physiologically-relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end bud-like structures. According to sequencing analysis of mammary gland RNA, PBDEs both augmented E2-facilitated cell proliferationgene expression changes and modulated immune regulation. To better elucidate the effects of E2 and PBDEs, single-cell RNA sequencing (scRNAseq) analysis was performed. In a definitive manner, E2 was found to induce Pgr expression in both Esr1+ and Esr1- cells. Significantly, molecular evidence was available to show functional differences among cells with differential expression of Esr1 and Pgr. The PBDEs + E2 treatment increased the number of double positive (Esr1+Pgr+) and Pgr only (Esr1-Pgr+) cells in both mature luminal epithelial and progenitor cells of luminal epithelialcells. Moreover, the combination increased the mammary gland population of M2 macrophages. The results help clarify how exposure to both E2 and endocrine disrupting chemicals like PBDEs during menopausal transition impact mammary gland structure. Ultimately, the findings advance understanding of how exposure can increase the risk of developing breast cancer.

2019-11-12 | GSE125272 | GEO

DNA Methylation analysis of polybrominated diphenyl ethers (PBDEs) treated hepatocellular carcinoma

Project description:DE-71, a commercial mixture of the polybrominated diphenyl ethers (PBDEs), is used as flame retardant and the potential exposure to PBDEs is an emerging public health concern. It has been clarified that long term exposure to PBDEs induces hepatocellular carcinoma in mouse. In this study, we analyzed how DE-71 impacts on DNA methylation in hepatocellular carcinoma.

2017-01-01 | GSE73326 | GEO

Perinatal exposure to an environmentally-relevant mixture of BFRs and ovarian gene expression in the adult rat

Project description:Brominated flame retardants (BFRs), including polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD), leach out from consumer products into the environment. Exposure to BFRs has been associated with effects on endocrine homeostasis. To test the hypothesis that in utero and lactational exposure to BFRs may affect the reproductive system of female offspring, adult female Sprague-Dawley rats were fed nominal doses (0, 0.06, 20, or 60 mg/kg/day) of a BFR dietary mixture formulated to mimic the levels of congeners in house dust from prior to mating until weaning. Vaginal opening and the day of first estrus occurred at a significantly earlier age among offspring from the 20 mg/kg/day BFR group, indicating that the onset of puberty was advanced. Histological analysis of ovaries from post-natal day 46 offspring revealed an increase in the incidence of multi-oocyte follicles. Toxicogenomics analysis of ovarian gene expression identified upstream regulators, including HIF1A, CREB1, EGF, the β-estradiol and PPARA pathways, predicted to be downregulated in the 20 mg/kg/day or the 60 mg/kg/day group and to contribute to the gene expression patterns observed. Thus, perinatal exposure to BFRs dysregulated ovarian folliculogenesis and signaling pathways that are fundamental for ovarian function.

2020-06-04 | GSE113000 | GEO

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