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.
journal_name
Environ Toxicol Pharmacoljournal_title
Environmental toxicology and pharmacologyauthors
De Haan LH,Halfwerk S,Hovens SE,De Roos B,Koeman JH,Brouwer Adoi
10.1016/1382-6689(95)00006-2subject
Has Abstractpub_date
1996-02-15 00:00:00pages
27-37issue
1eissn
1382-6689issn
1872-7077pii
1382-6689(95)00006-2journal_volume
1pub_type
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