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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE8588 | GEO | 2008/12/25

SECONDARY ACCESSION(S): PRJNA101743

REPOSITORIES: GEO

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Transcription profiling of human H295R adrenocortical carcinoma cells to investigate OH-PBDE-induced gene expression

Project description:Affymetrix high-density oligonucleotide microarray analysis was performed to analyse hydroxylated polybrominated diphenyl ethers (OH-PBDE)-induced gene expression changes in H295R adrenocortical carcinoma cells. Cells were treated with growth medium in the presence or absence of 10 µM 2-OH-BDE47 or 2-OH-BDE85 for 24 hours before the gene expression changes were investigated. Experiment Overall Design: Gene expression changes in response to hydroxylated polybrominated diphenyl ethers (OH-PBDEs) were analysed by Microarray technology in H295R adrenocortical carcinoma cells. Cells were treated with 10 µM of 2-OH-BDE47 or 2-OH-BDE85 (or growth medium alone) for 24 hours before the OH-PBDE-induced gene expression changes were investigated. Control, 2-OH-BDE47- and 2-OH-BDE85-treated samples were collected from three independent experiments each.

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