Determination of aryl hydrocarbon receptor activation potential (toxic potential) of polyhalogenated carbazole in rat hepatoma cell line H4IIE

Abstract

Polyhalogenated carbazoles (PHCZs) are a new class of environmental pollutants with similar structure and dioxins and have some dioxins-like toxic effects in different animal models. The main target of dioxins and dioxin-like compounds in the cell is the aromatic hydrocarbon receptor AHR (also known as the dioxin receptor), which produces a series of toxic effects by activating AHR. Therefore, the PHCZs may also have dioxin-like toxicity; however, there are very few studies on the AHR activation potential (toxic potential) of PHCZs. This study tested various PHCZs using the transient transfection-based luciferase reporter gene assay in the rat hepatoma cell line H4IIE to reflect activation/toxic potential in rat liver. It was found that the activation, at 1▒μM concentration, was ordered as: 2367CCZ > 1368BCZ > 27BCZ > 136BCZ > other. There were also differences between congeners or different halogen substitutions. Alternatively, the EC50 method is also used as a supplementary method to compare the activation potency, with the EC50 of 2367CCZ, 1368BCZ, and 1368CCZ being 4.08E-08, 4.11E-07, and 2.15E-06, respectively. Therefore, transient transfection-based luciferase reporter gene assay in H4IIE cells can effectively conduct the toxicity assessment of PHCZs and suggest that other species-specific toxicity assessments can be conducted using cell lines of other species.