Cytotoxicity and gene expression profiling of two hydroxylated polybrominated diphenyl ethers in human H295R adrenocortical carcinoma cells.

2.50
Hdl Handle:
http://hdl.handle.net/10146/83693
Title:
Cytotoxicity and gene expression profiling of two hydroxylated polybrominated diphenyl ethers in human H295R adrenocortical carcinoma cells.
Authors:
Song, Renfang; Duarte, Tiago L.; Almeida, Gabriela M.; Farmer, Peter B.; Cooke, Marcus S.; Zhang, Wenbing; Sheng, Guoying; Fu, Jiamo; Jones, George D.D.
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.
Citation:
Toxicol. Lett. 2009, 185 (1):23-31
Journal:
Toxicology letters
Issue Date:
25-Feb-2009
URI:
http://hdl.handle.net/10146/83693
DOI:
10.1016/j.toxlet.2008.11.011
PubMed ID:
19095052
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCR-4V17CPC-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=365d8e3357b0411a15182f0219394ccd
Type:
Article
Language:
en
ISSN:
0378-4274
Sponsors:
The 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.].
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorSong, Renfangen
dc.contributor.authorDuarte, Tiago L.en
dc.contributor.authorAlmeida, Gabriela M.en
dc.contributor.authorFarmer, Peter B.en
dc.contributor.authorCooke, Marcus S.en
dc.contributor.authorZhang, Wenbingen
dc.contributor.authorSheng, Guoyingen
dc.contributor.authorFu, Jiamoen
dc.contributor.authorJones, George D.D.en
dc.date.accessioned2009-10-07T07:16:45Z-
dc.date.available2009-10-07T07:16:45Z-
dc.date.issued2009-02-25-
dc.identifier.citationToxicol. Lett. 2009, 185 (1):23-31en
dc.identifier.issn0378-4274-
dc.identifier.pmid19095052-
dc.identifier.doi10.1016/j.toxlet.2008.11.011-
dc.identifier.urihttp://hdl.handle.net/10146/83693-
dc.description.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.en
dc.description.sponsorshipThe 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.].en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCR-4V17CPC-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=365d8e3357b0411a15182f0219394ccden
dc.subjectOH-PBDEen
dc.subjectH295R adrenocortical carcinoma cellsen
dc.subjectToxicityen
dc.subjectEndoplasmic reticulum stressen
dc.subjectUnfolded protein responseen
dc.subject.meshAdrenal Cortex Neoplasms-
dc.subject.meshAdrenocortical Carcinoma-
dc.subject.meshCell Cycle-
dc.subject.meshCell Line, Tumor-
dc.subject.meshCell Proliferation-
dc.subject.meshCell Survival-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshEndoplasmic Reticulum-
dc.subject.meshGene Expression Profiling-
dc.subject.meshHalogenated Diphenyl Ethers-
dc.subject.meshHumans-
dc.titleCytotoxicity and gene expression profiling of two hydroxylated polybrominated diphenyl ethers in human H295R adrenocortical carcinoma cells.en
dc.typeArticleen
dc.identifier.journalToxicology lettersen

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