Show simple item record

dc.contributor.authorSchlezinger, Jennifer J.
dc.contributor.authorBernard, Pamela L.
dc.contributor.authorHaas, Amelia
dc.contributor.authorGrandjean, Philippe
dc.contributor.authorWeihe, Pal
dc.contributor.authorSherr, David H.
dc.date.accessioned2010-11-29T18:34:58Z
dc.date.issued2009
dc.identifier.citationSchlezinger, Jennifer J., Pamela L. Bernard, Amelia Haas, Philippe Grandjean, Pal Weihe, and David H. Sherr. 2010. Direct assessment of cumulative aryl hydrocarbon receptor agonist activity in sera from experimentally exposed mice and environmentally exposed humans. Environmental Health Perspectives 118(5): 693-698.en_US
dc.identifier.issn0091-6765en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4592391
dc.description.abstractBackground: Aryl hydrocarbon receptor (AhR) ligands adversely affect many biological processes. However, assessment of the significance of human exposures is hampered by an incomplete understanding of how complex mixtures affect AhR activation/inactivation. Objectives: These studies used biological readouts to provide a broader context for estimating human risk than that obtained with serum extraction and gas chromatography/mass spectroscopy (GC/MS)-based assays alone. Methods: AhR agonist activity was quantified in sera from dioxin-treated mice, commercial human sources, and polychlorinated biphenyl (PCB)–exposed Faroe Islanders using an AhR-driven reporter cell line. To validate relationships between serum AhR agonist levels and biological outcomes, AhR agonist activity in mouse sera correlated with toxic end points. AhR agonist activity in unmanipulated (“neat”) human sera was compared with these biologically relevant doses and with GC/MS-assayed PCB levels. Results: Mouse serum AhR agonist activity correlated with injected dioxin dose, thymic atrophy, and heptomegaly, validating the use of neat serum to assess AhR agonist activity. AhR agonist activity in sera from Faroe Islanders varied widely, was associated with the frequency of recent pilot whale dinners, but did not correlate with levels of PCBs quantified by GC/MS. Surprisingly, significant “baseline” AhR activity was found in commercial human sera. Conclusions: An AhR reporter assay revealed cumulative levels of AhR activation potential in neat serum, whereas extraction may preclude detection of important non-dioxin-like biological activity. Significant levels of AhR agonist activity in commercial sera and in Faroe Islander sera, compared with that from experimentally exposed mice, suggest human exposures that are biologically relevant in both populations.en_US
dc.language.isoen_USen_US
dc.publisherNational Institute of Environmental Health Sciencesen_US
dc.relation.isversionofdoi:10.1289/ehp.0901113en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866687/pdf/en_US
dash.licenseLAA
dc.subjectaryl hydrocarbon receptoren_US
dc.subjectdioxin toxicityen_US
dc.subjectFaroe Islandsen_US
dc.subjecthuman serumen_US
dc.subjectimmunotoxicityen_US
dc.subjectpolychlorinated biphenylen_US
dc.titleDirect Assessment of Cumulative Aryl Hydrocarbon Receptor Agonist Activity in Sera from Experimentally Exposed Mice and Environmentally Exposed Humansen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalEnvironmental Health Perspectivesen_US
dash.depositing.authorGrandjean, Philippe
dc.date.available2010-11-29T18:34:58Z
dash.affiliation.otherSPH^Environmental+Occupational Medicine+Epien_US
dc.identifier.doi10.1289/ehp.0901113*
dash.contributor.affiliatedWeihe, Pal
dash.contributor.affiliatedGrandjean, Philippe
dc.identifier.orcid0000-0003-4046-9658


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record