title: Species-specific relative AHR1 binding affinities of 2,3,4,7,8-pentachlorodibenzofuran explain avian species differences in its relative potency.
abstract: Results of recent studies showed that 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are equipotent in domestic chicken (Gallus gallus domesticus) while PeCDF is more potent than TCDD in ring-necked pheasant (Phasianus colchicus) and Japanese quail (Coturnix japonica). To elucidate the mechanism(s) underlying these differences in relative potency of PeCDF among avian species, we tested the hypothesis that this is due to species-specific differential binding affinity of PeCDF to the aryl hydrocarbon receptor 1 (AHR1). Here, we modified a cell-based binding assay that allowed us to measure the binding affinity of dioxin-like compounds (DLCs) to avian AHR1 expressed in COS-7 (fibroblast-like cells). The results of the binding assay show that PeCDF and TCDD bind with equal affinity to chicken AHR1, but PeCDF binds with greater affinity than TCDD to pheasant (3-fold) and Japanese quail (5-fold) AHR1. The current report introduces a COS-7 whole-cell binding assay and provides a mechanistic explanation for differential relative potencies of PeCDF among species of birds.
authors.affiliation: Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada; Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3, Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Farmahin
authors.affiliation: Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3, Canada.
authors.forename: Stephanie P
authors.initials: SP
authors.lastname: Jones
authors.affiliation: Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3, Canada.
authors.forename: Doug
authors.initials: D
authors.lastname: Crump
authors.affiliation: Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Hahn
authors.affiliation: Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada; Department of Zoology and Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA; Department of Biology & Chemistry, City University of Hong Kong, Kowloon, Hong Kong, SAR, China.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Zwiernik
authors.affiliation: Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Bursian
authors.affiliation: Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada; Environment Canada, National Wildlife Research Centre, Ottawa, Ontario K1A 0H3, Canada. Electronic address: Sean.Kennedy@ec.gc.ca.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000378:metabolism* / Q000506:poisoning; D001717:Birds / Q000378:metabolism*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004147:Dioxins / Q000378:metabolism / Q000506:poisoning; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000506:poisoning; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D001572:Benzofurans; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C038890:2,3,4,7,8-pentachlorodibenzofuran
keywords: Aryl hydrocarbon receptor; Bird; COS-7 cells; Cell-based binding assay; Dioxin; PeCDF; TCDD