ToxSci Advance Access originally published online on September 12, 2008
Toxicological Sciences 2008 106(2):479-487; doi:10.1093/toxsci/kfn196
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Effects of Hexabromocyclododecane and Polybrominated Diphenyl Ethers on mRNA Expression in Chicken (Gallus domesticus) Hepatocytes
Environment Canada, National Wildlife Research Centre, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1A 0H3
1To whom correspondence should be addressed. Fax: 1-613-998-0458. E-mail: doug.crump{at}ec.gc.ca.
Received July 4, 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 end points of exposure are limited. An in vitro approach was used to compare concentration-dependent effects of HBCD and the commercial penta-brominated diphenyl ether 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 (30–100µM). Real-time RT-PCR assays were developed to quantify changes in mRNA abundance of genes associated with chicken xenobiotic-sensing orphan nuclear receptor activation, the thyroid hormone (TH) pathway, and lipid regulation. Exposure to 
1µM HBCD- and HBCD-TM resulted in significant upregulation of cytochrome P450 (CYP) 2H1 (fourfold to sevenfold) and CYP3A37 (5- to 30-fold) at 24 and 36 h. In contrast, 30µM DE-71 caused a twofold increase of CYP2H1 only. UGT1A9 expression was only upregulated by HBCD- to a maximum of fourfold at 1µM. Transthyretin, thyroid hormone–responsive spot 14-, and liver fatty acid–binding protein were all significantly downregulated (up to sevenfold) for cells exposed to 1µM HBCD- and HBCD-TM. DE-71 also downregulated these three target genes twofold to fivefold at concentrations 3µM. Taken together, our results indicate that xenobiotic-metabolizing enzymes and genes associated with the TH 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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