Cytotoxicity and gene expression profiling of two hydroxylated polybrominated diphenyl ethers in human H295R adrenocortical carcinoma cells.
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Duarte, Tiago L.
Almeida, Gabriela M.
Farmer, Peter B.
Cooke, Marcus S.
Jones, George D.D.
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AbstractPolybrominated 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.
CitationToxicol. Lett. 2009, 185 (1):23-31
SponsorsThe authors thank Ms. Jennifer Higgins and Ms. Rachel Kwok for their assistance with the statistical analysis. This work was supported by the National Natural Scientific Foundation of China [NSFC-40590390 to J.F.] and partly supported by the National Natural Scientific Foundation of China [NSFC-40590393 to J.F.]; the Chinese Academy of Sciences [KZCX2-YW-403 to J.F., O733241001 to R.S.]; and ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility) a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” [513943 to P.B.F., M.S. & G.D.D.J.]. Comet assay studies in the laboratory of G.D.D.J. were supported by Cancer Research UK [C13560/A46 to G.D.D.J.]; and Fellowships from the Hope Foundation [to G.D.D.J.].