Assessment of Ah receptor transcriptional activity mediated by halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) in human and mouse cell systems

ABSTRACTPolybrominated and mixed bromo/chloro dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) are emerging environmental contaminants of concern. Thus far, an understanding of the toxicological behavior of these chemical species and their impact upon human health is incomplete. Here we utilized human and mouse hepatocellular carcinoma cell lines to examine the ability of differentially halogenated PXDD/F congeners to induce aryl hydrocarbon receptor (AHR)-mediated transcriptional activity. Dose-response experiments in reporter cell lines identified varied potencies among differentially halogenated PXDD/F isomers by comparison of EC50 values relative to the prototypical AHR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Brominated PXDD/F species displayed reduced capacity to activate the mouse AHR, compared to TCDD. Only BrCl3 dibenzo-p-dioxin was found to have a greater relative potency than TCDD to induce human AHR transcriptional activity. Human cells required ∼10–29-fold higher ligand concentration...