title: Cytotoxicity and gene expression profiling of two hydroxylated polybrominated diphenyl ethers in human 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.
authors.affiliation: Department of Cancer Studies & Molecular Medicine, University of Leicester, University Road, Leicester LE1 7RH, UK.
authors.forename: Renfang
authors.initials: R
authors.lastname: Song
authors.forename: Tiago L
authors.initials: TL
authors.lastname: Duarte
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Almeida
authors.forename: Peter B
authors.initials: PB
authors.lastname: Farmer
authors.forename: Marcus S
authors.initials: MS
authors.lastname: Cooke
authors.forename: Wenbing
authors.initials: W
authors.lastname: Zhang
authors.forename: Guoying
authors.initials: G
authors.lastname: Sheng
authors.forename: Jiamo
authors.initials: J
authors.lastname: Fu
authors.forename: George D D
authors.initials: GD
authors.lastname: Jones
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000473:pathology*; D018268:Adrenocortical Carcinoma / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects; D020869:Gene Expression Profiling; D055768:Halogenated Diphenyl Ethers / Q000378:metabolism / Q000633:toxicity*; D006801:Humans
chemical_list: D055768:Halogenated Diphenyl Ethers