Predicting the Sensitivity of Avian Species to the Embryotoxic Effects of Polychlorinated Biphenyls (PCBs) Using 'in vitro' Approaches

Abstract

The goal of this thesis was to use a luciferase reporter gene (LRG) assay in order to predict avian species sensitivity to the toxic effects of polychlorinated biphenyl (PCB) congeners 126, 77, 105 and 118 based on their aryl hydrocarbon receptor 1 (AHR1) ligand binding domain (LBD) sequence. These results were then compared to ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA expression measured in three model species. The amino acid residues at positions 324 and 380 in the AHR1 LBD are the major determinants of avian species sensitivity to PCBs. Both LRG and EROD activity were significantly correlated with embryolethality and were better predictors of PCB-induced embryolethality than CYP1A4/5 mRNA expression. These results support the hypothesis that the LRG assay in combination with a species’ AHR1 LBD sequence can be used to predict PCB-induced embryolethality in potentially any avian species of interest without the use of lethal methods.