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ToxSci Advance Access originally published online on July 17, 2009
Toxicological Sciences 2009 111(2):311-320; doi:10.1093/toxsci/kfp160
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Effects of 18 Perfluoroalkyl Compounds on mRNA Expression in Chicken Embryo Hepatocyte Cultures

Nathan J. Hickey, Doug Crump, Stephanie P. Jones and Sean W. Kennedy1

Environment Canada, National Wildlife Research Centre, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1A 0H3

1 For correspondence via fax: 1-613-998-0458. E-mail: sean.kennedy{at}ec.gc.ca.

Received March 26, 2009; accepted July 10, 2009


  Abstract

Many studies have characterized the effects of perfluoroalkyl compounds (PFCs) in mammalian species, but limited information exists on the effects of PFCs in birds. PFCs have been detected in serum and liver of avian wildlife worldwide. While the molecular mechanisms have yet to be elucidated in detail, PFCs alter lipid metabolism through peroxisome proliferation, xenobiotic metabolism by activating the cytochrome P450 (CYP) system, and serum cholesterol levels by inducing or repressing key genes. Here, we employed a simple messenger RNA (mRNA) screening method using quantitative PCR to assess the effects of PFCs on mRNA expression in chicken embryo hepatocytes (CEH). CEH cultures were treated with perfluoroalkyl sulfonates and perfluoroalkyl carboxylates of varying chain lengths and linear or technical grade potassium perfluoro-1-octane sulfonate (L-PFOS and T-PFOS). T-PFOS comprised 80% perfluorooctane sulfonate isomers (62% linear) and various PFCs and inorganic salts. Relative mRNA expression levels of the following genes were examined: acyl-CoA oxidase (ACOX), liver fatty acid–binding protein (L-FABP), CYP1A4/1A5 and CYP4B1, 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase, and sterol regulatory element–binding protein 2 (SREBP2). Compared to L-PFOS, T-PFOS altered the mRNA expression level of more genes and produced greater fold changes. L-FABP was upregulated by PFCs greater than or equal to eight carbons, while CYPs were upregulated by PFCs less than or equal to eight carbons. ACOX, HMG-CoA, and SREBP2 showed little to no change following PFC exposure. This study is the first to expose CEH cultures to multiple PFCs in vitro and demonstrates that exposure to PFC solutions of different isomeric content or chain length causes variable transcriptional responses.

Key Words: perfluoroalkyl compounds; gene expression; hepatocyte; chicken; screening tool.


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