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In vitro function of the aryl hydrocarbon receptor predicts in vivo sensitivity of oviparous vertebrates to dioxin-like compounds
Citation:
Doering, J., S. Wiseman, A. Alcaraz, J. Giesy, AND M. Hecker. In vitro function of the aryl hydrocarbon receptor predicts in vivo sensitivity of oviparous vertebrates to dioxin-like compounds. SETAC Midwest Chapter, Minneapolis, MN, March 20 - 22, 2017.
Impact/Purpose:
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Description:
Differences in sensitivity to dioxin-like compounds (DLCs) among species and taxa presents a major challenge to ecological risk assessments. Activation of the aryl hydrocarbon receptor (AHR) regulates adverse effects associated with exposure to DLCs in vertebrates. Prior investigations demonstrated that sensitivity to activation of the AHR1 (50% effect concentration; EC50) in an in vitro luciferase reporter gene (LRG) assay was predictive of the sensitivity of embryos (lethal dose to cause 50% lethality; LD50) across all species of birds for all DLCs. However, nothing was known about whether sensitivity to activation of the AHR is predictive of sensitivity of embryos of fishes to DLCs. Therefore, this study investigated in vitro sensitivities of AHR1s and AHR2s to the model DLC, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), among eight species of fish of known sensitivities of embryos to TCDD. AHR1s and AHR2s of all fishes were activated by TCDD in vitro. There was no significant linear relationship between in vitro sensitivity of AHR1 and in vivo sensitivity among the investigated fishes (R2 = 0.33, p = 0.23). However, there was a significant linear relationship between in vitro sensitivity of AHR2 and in vivo sensitivity among the investigated fishes (R2 = 0.97, p = < 0.0001). The linear relationship between in vitro sensitivity of AHR2 and in vivo sensitivity of embryos among fishes was compared to the previously generated linear relationship between in vitro sensitivity of AHR1 and in vivo sensitivity of embryos among birds. The slope and y-intercept for the linear relationship for AHR2 of fishes is not statistically different (p = 0.11 and p = 0.052, respectively) from the slope and y-intercept for the linear relationship for AHR1 of birds. This suggests that the same quantitative linear relationship is present between in vitro activation of the AHR and in vivo sensitivity of embryos in these two evolutionarily distant groups of oviparous taxa. The linear relationship between in vitro sensitivity of AHR1 and in vivo sensitivity of embryos among birds is well established across different DLCs. Therefore, all in vitro and in vivo data for fishes and birds across all DLCs was combined into a single significant linear relationship (R2 = 0.87; p = < 0.0001). It is anticipated that this linear relationship can be used to predict the in vivo sensitivity of embryos for any species of oviparous vertebrate to any DLC for application to ecological risk assessment.