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Predicting the sensitivity of fishes to dioxin-like compounds: possible role of the aryl hydrocarbon receptor (AhR) ligand binding domain
Authors:Jon A Doering  John P Giesy  Steve Wiseman  Markus Hecker
Institution:1. Toxicology Centre, University of Saskatchewan, Toxicology Centre, 44 Campus Drive, Saskatoon, SK, Canada, S7N 5B3
2. Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5B3
3. Department of Zoology, Centre for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA
4. Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong, China
5. School of Biological Sciences, The University of Hong Kong, Hong Kong, China
6. State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing, China
7. School of the Environment and Sustainability, University of Saskatchewan, Saskatoon, SK, Canada
Abstract:Dioxin-like compounds are chronically toxic to most vertebrates. However, dramatic differences in sensitivity to these chemicals exist both within and among vertebrate classes. A recent study found that in birds, critical amino acid residues in the aryl hydrocarbon receptor (AhR) ligand binding domain are predictive of sensitivity to dioxin-like compounds in a range of species. It is currently unclear whether similar predictive relationships exist for fishes, a group of animals at risk of exposure to dioxin-like compounds. Effects of dioxin-like compounds are mediated through the AhR in fishes and birds. However, AhR dynamics are more complex among fishes. Fishes possess AhRs that can be grouped within at least three distinct clades (AhR1, AhR2, AhR3) with each clade possibly containing multiple isoforms. AhR2 has been shown to be the active form in most teleosts, with AhR1 not binding dioxin-like compounds. The role of AhR3 in dioxin-like toxicity has not been established to date and this clade is only known to be expressed in some cartilaginous fishes. Furthermore, multiple mechanisms of sensitivity to dioxin-like compounds that are not relevant in birds could exist among fishes. Although, at this time, deficiencies exist for the development of such a predictive relationship for application to fishes, successfully establishing such relationships would offer a substantial improvement in assessment of risks of dioxin-like compounds for this class of vertebrates. Elucidation of such relationships would provide a mechanistic foundation for extrapolation among species to allow the identification of the most sensitive fishes, with the ultimate goal of the prediction of risk posed to endangered species that are not easily studied.
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