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dc.contributor.authorHill, Katie L.
dc.contributor.authorMortensen, Åse-Karen
dc.contributor.authorTeclechiel, Daniel
dc.contributor.authorWillmore, William G.
dc.contributor.authorSylte, Ingebrigt
dc.contributor.authorJenssen, Bjørn Munro
dc.contributor.authorLetcher, Robert James
dc.date.accessioned2019-04-03T11:06:09Z
dc.date.available2019-04-03T11:06:09Z
dc.date.issued2017-12-28
dc.description.abstractTetradecabromo-1,4-diphenoxybenzene (TeDB-DiPhOBz) is a highly brominated additive flame retardant (FR). Debrominated photodegradates of TeDBDiPhOBz are hydroxylated <i>in vitro</i> in liver microsomal assays based on herring gulls (<i>Larus argentatus</i>), including one metabolite identified as 4<i>″</i>-OH-2,2<i>′</i>,2<i>″</i>,4-tetrabromo-DiPhOBz. Chemically related methoxylated tetra- to hexabromo-DiPhOBzs are known contaminants in herring gulls. Collectively, nothing is currently known about biological effects of these polybrominated (PB) DiPhOBz-based compounds. The present study investigated the potential thyroidogenicity of 2,2<i>′,2</i>″,4-tetrabromo-(TB)-DiPhOBz along with its <i>para</i>-methoxy (MeO)- and hydroxy-(OH)-analogues, using an <i>in vitro</i> competitive protein binding assay with the human thyroid hormone (TH) transport proteins transthyretin (hTTR) and albumin (hALB). This model <i>para</i>-OH-TB-DiPhOBz was found to be capable of competing with thyroxine (T4) for the binding site on hTTR and hALB. <i>In silico</i> analyses were also conducted using a 3D homology model for gull TTR, to predict whether these TB-DiPhOBz-based compounds may also act as ligands for an avian TH transport protein despite evolutionary differences with hTTR. This analysis found all three TB-DiPhOBz analogues to be potential ligands for gull TTR and have similar binding efficacies to THs. Results indicate structure-related differences in binding affinities of these ligands and suggest there is potential for these contaminants to interact with both mammalian and avian thyroid function.en_US
dc.description.sponsorshipChemicals Management Plan CMP; Environment and Climate Change Canada) National and Engineering Science Research Council (NSERC) of Canada NSERC CREATE Program Norwegian University of Science and Technologyen_US
dc.descriptionAccepted manuscript version. Published version available at <a href=https://doi.org/10.1021/acs.est.7b04617>https://doi.org/10.1021/acs.est.7b04617. </a>en_US
dc.identifier.citationHill, K.L., Mortensen, Å-K., Teclechiel, D., Willmore, W.G., Sylte, I., Jenssen, B.M. & Letcher, R.J. (2018). <i>In Vitro</i> and <i>in Silico</i> Competitive Binding of Brominated Polyphenyl Ether Contaminants with Human and Gull Thyroid Hormone Transport Proteins. <i>Environmental Science and Technology, 52</i>(3), 1533-1541. https://doi.org/10.1021/acs.est.7b04617en_US
dc.identifier.cristinIDFRIDAID 1592289
dc.identifier.doi10.1021/acs.est.7b04617
dc.identifier.issn0013-936X
dc.identifier.issn1520-5851
dc.identifier.urihttps://hdl.handle.net/10037/15155
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.journalEnvironmental Science and Technology
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/POLARPROG/268419/Norway/The Ecological Relevance of Thyroid Disruptive Chemicals in Arctic Glaucous Gulls//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Mathematics and natural science: 400::Zoology and botany: 480en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480en_US
dc.titleIn Vitro and in Silico Competitive Binding of Brominated Polyphenyl Ether Contaminants with Human and Gull Thyroid Hormone Transport Proteinsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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