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

作者：Organtini Kari L; Hubbard Troy D; Perdew Gary H; Dorman Frank L^*

来源：Journal of Environmental Science and Health - Part A: Toxic/Hazardous Substances & Environmental Engineering , 2017, 52(14): 1295-1302.

DOI：10.1080/10934529.2017.1362290

• Aryl hydrocarbon receptor
• AHR
• dibenzofurans
• dibenzo-p-dioxins
• mixed halogenated
• PXDD
• F

Polybrominated 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 approximate to 10-29-fold higher ligand concentrations to induce analogous AHR activity, relative to mouse cells. Decreased sensitivity of the human AHR to brominated dibenzofuran congeners directly corresponded to the number of bromine functional groups. Mixtures of these compounds exhibited an additive effect on AHR activation. The data also support the inclusion of mixed halogenated dibenzo-p-dioxins and dibenzofurans into routine environmental screening procedures as well as more thorough toxicological characterization of PXDD/Fs.

• 出版日期2017