Journal Article

Effects of Hexabromocyclododecane and Polybrominated Diphenyl Ethers on mRNA Expression in Chicken (<i>Gallus domesticus</i>) Hepatocytes

Doug Crump, Suzanne Chiu, Caroline Egloff and Sean W. Kennedy

in Toxicological Sciences

Volume 106, issue 2, pages 479-487
Published in print December 2008 | ISSN: 1096-6080
Published online September 2008 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfn196
Effects of Hexabromocyclododecane and Polybrominated Diphenyl Ethers on mRNA Expression in Chicken (Gallus domesticus) Hepatocytes

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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-α, 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-α 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-α to a maximum of fourfold at ≥ 1μM. Transthyretin, thyroid hormone–responsive spot 14-α, and liver fatty acid–binding protein were all significantly downregulated (up to sevenfold) for cells exposed to ≥ 1μM HBCD-α 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.

Keywords: gene expression; HBCD; PBDE; thyroid hormone; phase I and II enzymes; avian

Journal Article.  5261 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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