ToxSci Advance Access published online on September 12, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn196
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Effects of hexabromocyclododecane (HBCD) and polybrominated diphenyl ethers (PBDEs) on mRNA expression in chicken (Gallus domesticus) hepatocytes
Environment Canada, National Wildlife Research Centre, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1A 0H3; suzanne.chiu{at}ec.gc.ca
Environment Canada, National Wildlife Research Centre, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1A 0H3; divavenere{at}gmail.com
Environment Canada, National Wildlife Research Centre, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1A 0H3; sean.kennedy{at}ec.gc.ca
* Environment Canada, National Wildlife Research Centre, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1A 0H3. To whom correspondence may be addressed doug.crump{at}ec.gc.ca.; Tel. 1-613-998-7383; fax: 1-613-998-0458.
Received July 4, 2008; revision received September 5, 2008; accepted September 7, 2008
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Abstract |
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Hexabromocyclododecane (HBCD) and polybrominated diphenyl ethers (PBDEs) are additive flame retardants used in a wide range of consumer products. Both compounds have been detected in free-living avian species but, toxicological and molecular endpoints of exposure are limited. An in vitro approach was used to compare concentration-dependent effects of HBCD and the commercial penta-BDE mixture DE-71 on cytotoxicity and mRNA expression in cultured hepatocytes derived from embryonic chickens. Neither HBCD-
, HBCD-technical mixture (TM) nor DE-71 effected hepatocyte viability at the highest concentrations assessed (30-100 µM). Real-time RT-PCR assays were developed to quantify changes in mRNA abundance of genes associated with chicken xenobiotic receptor (CXR) activation, the thyroid hormone pathway and lipid regulation. Exposure to 
1µM HBCD- and HBCD-TM resulted in significant up-regulation of CYP2H1 (4-7 fold) and CYP3A37 (5-30 fold) at 24 and 36 hours. In contrast, 30µM DE-71 caused a 2-fold increase of CYP2H1 only. UGT1A9 expression was only up-regulated by HBCD- to a maximum of 4-fold at 1µM. Transthyretin, thyroid hormone-responsive spot 14-, and liver fatty acid binding protein were all significantly down-regulated (up to 7-fold) for cells exposed to 1µM HBCD- and HBCD-TM. DE-71 also down-regulated these three target genes 2-5 fold at concentrations 3µM. Taken together, our results indicate that xenobiotic metabolizing enzymes and genes associated with the thyroid hormone pathway and lipid regulation are vulnerable to HBCD and DE-71 administration in cultured avian hepatocytes and might be useful molecular markers of exposure.
Key Words: Gene expression; HBCD; PBDE; thyroid hormone; phase I and II enzymes; avian.
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