Title: Antagonistic effects of mono- and di-ortho-substituted PCBs in the EROD activity and the luciferase reporter gene assay in vitro

Auteur(s): Van der Plas SA ; Gibbs CM ; Brouwer A ;  ; 

Year: 1998

Journal: Organohalogen Compounds

Subject(s): EROD ; PCB ; PCBs ; Reporter gene ; Reporter gene assay ; polychlorinated ; polychlorinated biphenyls ; Polychlorinated biphenyl ; polychlorinated dibenzofurans ; polyhalogenated aromatic hydrocarbons ; environment ; Ah receptor ; Interaction ; Luciferase ; CALUX ;  ; 

Summary: Polychlorinated biphenyls (PCBs), polychlorodibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and other polyhalogenated aromatic hydrocarbons (pHAHs) are present in the environment as complex mixtures. The toxic equivalency factor (TEF) concept has been developed for risk management purposes and allows to calculate the toxic potency of PHAH mixtures based on the assumptions that all dioxin-like congeners act through the same Ah receptor based mechanism and that the effects of individual compounds are additive. However, in the past it bas already been shown that some non-dioxin di-ortho substituted PCBs possess a low binding affinity for the Ah receptor and interactions between congeners have been reported both in vivo and in vitro. Besides, Besselink el al. reported an in vitro competitive inhibition of the CYP1A activity by several PCB congeners in rat liver microsomes. The objective of this study was to determine whether mono- and di-ortho PCBs antagonize the AhR-mediated, 2,3,7,8,-TCDD induced ethoxyresorufin-O-deethylase (EROD) activity with different potencies and different maximum levels. To exclude the possibility of competitive inhibition of the CYP1A activity, combinations of congeners were also tested in the AhR mediated luciferase reporter gene (CALUX) assay.