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.
Highlights
Polybrominated biphenyl ethers (PBDEs) are synthetic compounds used as flame retardants in a variety of construction materials, textiles, and polymers for electronic equipment
When cells were incubated with 10 μM 2-OH-BDE85 in the presence of the DNA repair inhibitors the slight increase in tail DNA observed at 24 h was not greater than that observed in control cells
Our data suggest that the toxicity of OH-pentabrominated diphenyl ether (PBDE) in H295R cells cannot be explained by a genotoxic mechanism
Summary
Polybrominated biphenyl ethers (PBDEs) are synthetic compounds used as flame retardants in a variety of construction materials, textiles, and polymers for electronic equipment. Exposure to PCBs is associated with adverse effects on human health. There is increasing concern about the potential endocrine-disrupting properties of brominated flame retardants and their derivatives, which could affect steroidogenic enzymes responsible for the biosynthesis of various steroid hormones, and eventually cause reproductive problems, cancer and other pathological conditions related to growth and development.
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