title: Inhibition of intercellular communication and induction of ethoxyresorufin-O-deethylase activity by polychlorobiphenyls, -dibenzo-p-dioxins and -dibenzofurans in mouse hepa1c1c7 cells.
abstract: Inhibition of intercellular communication (IC) between hepa1c1c7 cells was used as a possible bioassay to predict tumor promoting potency of polyhalogenated aromatic hydrocarbons (PAHs). Relative potencies with regard to 2,3,7,8-TCDD to inhibit IC and to induce cytochrome P450IA1/2 (EROD) in these hepa1c1c7 cells were compared in order to investigate the possible role of the Ah receptor (AhR). For the PCDD/F and the co-planar PCB congeners relative potencies of both responses were within the same range. However, the mono-ortho PCBs, 2,3,3',4,4'-PeCB, 2,3,4,4',5-PeCB, 2,3',4,4',5-PeCB and 2,3,3',4,4',5,5'-HxCB showed a 30-1300 times higher potency to inhibit IC compared to EROD induction activity. These potency differences were even more pronounced for the di-ortho PCBs, 2,2',5,5'-TeCB and 2,2',3,3',4,4'-HxCB. The data presented here indicate that for IC inhibition by these non-planar PCBs a non-AhR mediated mechanism, with a different structure-activity relationship may be responsible. Given the high IC inhibition potency of mono- and di-ortho PCBs and their abundancy in environmental mixtures, the mono- and di-ortho PCBs may contribute for a major part to the total tumor promoting potency of complex mixtures relevant to human exposure. Using the traditional TEF values, these compounds do not account for much toxic potency in a mixture, which may imply that the tumor promotion potential is not covered by the commonly derived TEF values.
authors.affiliation: Department of Toxicology, Agricultural University Wageningen, P.O. Box 8000, 6700 EA Wageningen, Netherlands.
authors.forename: L H
authors.initials: LH
authors.lastname: De Haan
authors.forename: S
authors.initials: S
authors.lastname: Halfwerk
authors.forename: S E
authors.initials: SE
authors.lastname: Hovens
authors.forename: B
authors.initials: B
authors.lastname: De Roos
authors.forename: J H
authors.initials: JH
authors.lastname: Koeman
authors.forename: A
authors.initials: A
authors.lastname: Brouwer