![]() For risk assessment purposes, the toxic potencies of individual DLCs are compared with the potency of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), which is generally considered to be the most potent compound within this class of chemicals ( Van den Berg et al., 1998,, 2006). Based on the available evidence, the domestic chicken ( Gallus gallus domesticus) is the most sensitive species to the toxic effects of DLCs. For example, sensitivity to the biochemical and toxic effects of some DLCs can vary up to 1000-fold among avian species ( Brunström, 1988 Head and Kennedy, 2010 Head et al., 2008 Hoffman et al., 1998). These results indicate promise for the use of AHR1 LBD amino acid sequences independently, or combined with the LRG assay, to predict avian species sensitivity to DLCs.ĭioxin, risk assessment, bird, Ah receptor, molecular toxicologyĭioxins and dioxin-like compounds (DLCs) share structural similarities and common mechanisms of biochemical and toxic action, but differences in sensitivity to DLCs exist among species and strains of animals. ![]() The results of the study revealed that (1) only amino acids at sites 324 and 380 affect the sensitivity of AHR1 expression constructs of the 86 avian species to DLCs and (2) in vitro luciferase activity of AHR1 constructs containing only the LBD of the species of interest is significantly correlated ( r 2 = 0.93, p < 0.0001) with in ovo toxicity data for those species. Site-directed mutagenesis, the LRG assay, and homology modeling highlighted the importance of each amino acid site in AHR1 sensitivity to 2,3,7,8-tetrachlorodibenzo- p-dioxin and other DLCs. In the present study, the AHR1 LBD sequences of 86 avian species were studied, and differences at amino acid sites 256, 257, 297, 324, 337, and 380 were identified. Those findings suggest that the AHR1 LBD sequence and the LRG assay can be used to predict avian species sensitivity to DLCs. We previously showed that LD 50 values, based on in ovo exposures to DLCs, were significantly correlated with in vitro EC 50 values obtained with a luciferase reporter gene (LRG) assay that measures AHR1-mediated induction of cytochrome P4501A in COS-7 cells transfected with avian AHR1 constructs. The sensitivity of avian species to the toxic effects of dioxin-like compounds (DLCs) varies up to 1000-fold among species, and this variability has been associated with interspecies differences in aryl hydrocarbon receptor 1 ligand-binding domain (AHR1 LBD) sequence.
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