TY - JOUR T1 - Analysis of Ah receptor pathway activation by brominated flame retardants JF - Chemosphere Y1 - 2004 A1 - Brown,D.J. A1 - Ilse Van Overmeire A1 - Goeyens,L. A1 - Michael Denison A1 - De Vito,M.J. A1 - Clark,G.C. KW - analysis KW - Animals KW - article KW - AS KW - at KW - Benzofurans KW - Bromine Compounds KW - chemistry KW - Comparative Study KW - consumer KW - contaminant KW - contaminants KW - Cytosol KW - detection KW - Dioxin KW - Dioxins KW - Dose-Response Relationship,Drug KW - drug effects KW - effective KW - Electrophoretic Mobility Shift Assay KW - environmental KW - ENVIRONMENTAL-SAMPLES KW - expression KW - Flame Retardants KW - gene KW - Genes KW - Guinea Pigs KW - im KW - interaction KW - IS KW - journal KW - Liver KW - Luciferases KW - metabolism KW - Oligonucleotides KW - Phosphorus KW - Phosphorus Radioisotopes KW - Polybrominated Biphenyls KW - Print KW - production KW - Radioisotopes KW - receptors KW - Receptors,Aryl Hydrocarbon KW - relative KW - Research KW - Research Support KW - response KW - result KW - results KW - risk KW - S KW - SAFETY KW - Sample KW - Samples KW - SB - IM KW - Signal Transduction KW - Still KW - study KW - System KW - toxicity KW - transduction KW - use KW - values AB - Brominated flame-retardants (BFRs) are used as additives in plastics to decrease the rate of combustion of these materials, leading to greater consumer safety. As the use of plastics has increased, the production and use of flame-retardants has also grown. Many BFRs are persistent and have been detected in environmental samples, raising concerns about the biological/toxicological risk associated with their use. Most BFRs appear to be non-toxic, however there is still some concern that these compounds, or possible contaminants in BFRs mixtures could interact with cellular receptors. In this study we have examined the interaction of decabromodiphenyl ether, Firemaster BP4A (tetrabromobisphenol A), Firemaster PHT4 (tetrabromophthalic anhydride), hexabromobenzene, pentabromotoluene, decabromobiphenyl, Firemaster BP-6 (2,2',4,4',5,5'-hexabromobiphenyl) and possible contaminants of BFR mixtures with the Ah receptor. Receptor binding and activation was examined using the Gel Retardation Assay and increased expression of dioxin responsive genes was detected using the reporter gene based CALUX assay. The results demonstrate the ability of BFRs to activate the AhR signal transduction pathway at moderate to high concentrations as assessed using both assays. AhR-dependent activation by BFRs may be due in part to contaminants present in commercial/technical mixtures. This was suggested by our comparative analysis of Firemaster BP-6 versus its primary component 2,2',4,4',5,5'-hexabromobiphenyl. Some technical mixtures of brominated flame-retardants contain brominated biphenyls, dioxins or dibenzofurans as contaminants. When tested in the CALUX assay these compounds were found to be equivalent to, or more active than their chlorinated analogues. Relative effective potency values were determined from dose response curves for these brominated HAHs VL - 55 CP - 11 U1 - 1906 M3 - http://dx.doi.org/10.1016/j.chemosphere.2003.10.019 ER -