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Title: Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity

Abstract

Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1 ligand binding domain sequence, were also shown to predict avian species sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a given species. The goals of the present study were to (1) characterize the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs 126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo hepatocytes and (2) compare these in vitro results to those previously generated by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA expression data support and complementmore » the findings of the LRG assay. CYP1A enzyme activity and mRNA expression were significantly correlated both with luciferase activity and in ovo toxicity induced by PCBs. Relative potency values were generally similar between the LRG and EROD assays and indicate that the relative potency of some PCBs may differ among species. -- Highlights: ► The chicken isn't the most sensitive species to CYP1A induction by PCB 105 and 118. ► The relative potency of PCBs differs between avian species. ► EROD activity was correlated with luciferase activity from the LRG assay. ► EROD activity was a better predictor of toxicity than CYP1A4/5 mRNA expression.« less

Authors:
 [1];  [1];  [2];  [2];  [2]
  1. Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 (Canada)
  2. Wellington Laboratories Inc., Research Division, Guelph, ON, Canada N1G 3chsM5 (Canada)
Publication Date:
OSTI Identifier:
22216016
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 266; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; CHICKENS; DIOXIN; EMBRYOS; ENZYME ACTIVITY; GENES; HYDROCARBONS; IN VITRO; LIGANDS; LIVER CELLS; LUCIFERASE; MESSENGER-RNA; NECK; POLYCHLORINATED BIPHENYLS; RECEPTORS; RISK ASSESSMENT; SENSITIVITY; TOXICITY

Citation Formats

Manning, Gillian E., E-mail: gmann017@uottawa.ca, Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3, Mundy, Lukas J., E-mail: lukas.mundy@ec.gc.ca, Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3, Crump, Doug, Jones, Stephanie P., E-mail: stephanie.jones@ec.gc.ca, Chiu, Suzanne, Klein, Jeff, Konstantinov, Alex, Potter, Dave, Kennedy, Sean W., E-mail: sean.kennedy@ec.gc.ca, and Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3. Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2012.10.030.
Manning, Gillian E., E-mail: gmann017@uottawa.ca, Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3, Mundy, Lukas J., E-mail: lukas.mundy@ec.gc.ca, Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3, Crump, Doug, Jones, Stephanie P., E-mail: stephanie.jones@ec.gc.ca, Chiu, Suzanne, Klein, Jeff, Konstantinov, Alex, Potter, Dave, Kennedy, Sean W., E-mail: sean.kennedy@ec.gc.ca, & Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3. Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity. United States. https://doi.org/10.1016/J.TAAP.2012.10.030
Manning, Gillian E., E-mail: gmann017@uottawa.ca, Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3, Mundy, Lukas J., E-mail: lukas.mundy@ec.gc.ca, Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3, Crump, Doug, Jones, Stephanie P., E-mail: stephanie.jones@ec.gc.ca, Chiu, Suzanne, Klein, Jeff, Konstantinov, Alex, Potter, Dave, Kennedy, Sean W., E-mail: sean.kennedy@ec.gc.ca, and Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3. 2013. "Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity". United States. https://doi.org/10.1016/J.TAAP.2012.10.030.
@article{osti_22216016,
title = {Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity},
author = {Manning, Gillian E., E-mail: gmann017@uottawa.ca and Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 and Mundy, Lukas J., E-mail: lukas.mundy@ec.gc.ca and Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3 and Crump, Doug and Jones, Stephanie P., E-mail: stephanie.jones@ec.gc.ca and Chiu, Suzanne and Klein, Jeff and Konstantinov, Alex and Potter, Dave and Kennedy, Sean W., E-mail: sean.kennedy@ec.gc.ca and Environment Canada, National Wildlife Research Centre, Ottawa, ON, Canada K1A 0H3},
abstractNote = {Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1 ligand binding domain sequence, were also shown to predict avian species sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a given species. The goals of the present study were to (1) characterize the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs 126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo hepatocytes and (2) compare these in vitro results to those previously generated by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA expression data support and complement the findings of the LRG assay. CYP1A enzyme activity and mRNA expression were significantly correlated both with luciferase activity and in ovo toxicity induced by PCBs. Relative potency values were generally similar between the LRG and EROD assays and indicate that the relative potency of some PCBs may differ among species. -- Highlights: ► The chicken isn't the most sensitive species to CYP1A induction by PCB 105 and 118. ► The relative potency of PCBs differs between avian species. ► EROD activity was correlated with luciferase activity from the LRG assay. ► EROD activity was a better predictor of toxicity than CYP1A4/5 mRNA expression.},
doi = {10.1016/J.TAAP.2012.10.030},
url = {https://www.osti.gov/biblio/22216016}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 266,
place = {United States},
year = {Tue Jan 01 00:00:00 EST 2013},
month = {Tue Jan 01 00:00:00 EST 2013}
}