Direct Assessment of Cumulative Aryl Hydrocarbon Receptor Agonist Activity in Sera from Experimentally Exposed Mice and Environmentally Exposed Humans
Background: 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...
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ftharvardudash:oai:dash.harvard.edu:1/4592391 2023-05-15T16:11:00+02:00 Direct Assessment of Cumulative Aryl Hydrocarbon Receptor Agonist Activity in Sera from Experimentally Exposed Mice and Environmentally Exposed Humans Schlezinger, Jennifer J. Bernard, Pamela L. Haas, Amelia Grandjean, Philippe Weihe, Pal Sherr, David H. 2009 application/pdf http://nrs.harvard.edu/urn-3:HUL.InstRepos:4592391 https://doi.org/10.1289/ehp.0901113 en_US eng National Institute of Environmental Health Sciences doi:10.1289/ehp.0901113 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866687/pdf/ Environmental Health Perspectives Schlezinger, 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. 0091-6765 http://nrs.harvard.edu/urn-3:HUL.InstRepos:4592391 aryl hydrocarbon receptor dioxin toxicity Faroe Islands human serum immunotoxicity polychlorinated biphenyl Journal Article 2009 ftharvardudash https://doi.org/10.1289/ehp.0901113 2022-04-04T12:43:10Z Background: 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. Version of Record Article in Journal/Newspaper Faroe Islands Harvard University: DASH - Digital Access to Scholarship at Harvard Faroe Islands Environmental Health Perspectives 118 5 693 698 |
institution |
Open Polar |
collection |
Harvard University: DASH - Digital Access to Scholarship at Harvard |
op_collection_id |
ftharvardudash |
language |
English |
topic |
aryl hydrocarbon receptor dioxin toxicity Faroe Islands human serum immunotoxicity polychlorinated biphenyl |
spellingShingle |
aryl hydrocarbon receptor dioxin toxicity Faroe Islands human serum immunotoxicity polychlorinated biphenyl Schlezinger, Jennifer J. Bernard, Pamela L. Haas, Amelia Grandjean, Philippe Weihe, Pal Sherr, David H. Direct Assessment of Cumulative Aryl Hydrocarbon Receptor Agonist Activity in Sera from Experimentally Exposed Mice and Environmentally Exposed Humans |
topic_facet |
aryl hydrocarbon receptor dioxin toxicity Faroe Islands human serum immunotoxicity polychlorinated biphenyl |
description |
Background: 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. Version of Record |
format |
Article in Journal/Newspaper |
author |
Schlezinger, Jennifer J. Bernard, Pamela L. Haas, Amelia Grandjean, Philippe Weihe, Pal Sherr, David H. |
author_facet |
Schlezinger, Jennifer J. Bernard, Pamela L. Haas, Amelia Grandjean, Philippe Weihe, Pal Sherr, David H. |
author_sort |
Schlezinger, Jennifer J. |
title |
Direct Assessment of Cumulative Aryl Hydrocarbon Receptor Agonist Activity in Sera from Experimentally Exposed Mice and Environmentally Exposed Humans |
title_short |
Direct Assessment of Cumulative Aryl Hydrocarbon Receptor Agonist Activity in Sera from Experimentally Exposed Mice and Environmentally Exposed Humans |
title_full |
Direct Assessment of Cumulative Aryl Hydrocarbon Receptor Agonist Activity in Sera from Experimentally Exposed Mice and Environmentally Exposed Humans |
title_fullStr |
Direct Assessment of Cumulative Aryl Hydrocarbon Receptor Agonist Activity in Sera from Experimentally Exposed Mice and Environmentally Exposed Humans |
title_full_unstemmed |
Direct Assessment of Cumulative Aryl Hydrocarbon Receptor Agonist Activity in Sera from Experimentally Exposed Mice and Environmentally Exposed Humans |
title_sort |
direct assessment of cumulative aryl hydrocarbon receptor agonist activity in sera from experimentally exposed mice and environmentally exposed humans |
publisher |
National Institute of Environmental Health Sciences |
publishDate |
2009 |
url |
http://nrs.harvard.edu/urn-3:HUL.InstRepos:4592391 https://doi.org/10.1289/ehp.0901113 |
geographic |
Faroe Islands |
geographic_facet |
Faroe Islands |
genre |
Faroe Islands |
genre_facet |
Faroe Islands |
op_relation |
doi:10.1289/ehp.0901113 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866687/pdf/ Environmental Health Perspectives Schlezinger, 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. 0091-6765 http://nrs.harvard.edu/urn-3:HUL.InstRepos:4592391 |
op_doi |
https://doi.org/10.1289/ehp.0901113 |
container_title |
Environmental Health Perspectives |
container_volume |
118 |
container_issue |
5 |
container_start_page |
693 |
op_container_end_page |
698 |
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1765996121631490048 |