PMID- 21893176 OWN - NLM STAT- MEDLINE DCOM- 20120118 LR - 20161125 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 207 IP - 1 DP - 2011 Nov 10 TI - In vitro and in ovo effects of four brominated flame retardants on toxicity and hepatic mRNA expression in chicken embryos. PG - 25-33 LID - 10.1016/j.toxlet.2011.08.015 [doi] AB - Some currently used brominated flame retardants (BFRs), such as hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO), bis(2-ethylhexyl)tetrabromophthalate (BEHTBP), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and decabromodiphenylethane (DBDPE), are persistent organic contaminants detected in various environmental matrices, including wild birds. Data on potential toxicological and molecular responses to exposure of these BFRs are lacking for avian species. A combined in vitro/in ovo approach was used to determine the concentration-dependent effects of these BFRs on overt toxicity and hepatic messenger RNA (mRNA) expression levels of 11 transcripts in (1) primary cultures of chicken embryonic hepatocytes (CEH; all four BFRs) and (2) chicken embryos (HCDBCO and BTBPE only). Neither hepatocyte viability nor embryonic pipping success were affected by the BFRs at any of the administered concentrations (CEH: 0.001-30 muM, egg injection: 0.1-10 mug/g nominal dose). In CEH, 10 muM HCDBCO induced cytochrome P450 2H1 (CYP2H1) and CYP3A37, while CYP1A4/5 were down-regulated at all tested concentrations. In contrast, only transthyretin was down-regulated by HCDBCO in embryonic liver. There was concordance between the BTBPE-induced transcriptional responses in vitro and in ovo for CYP1A4/5 (up-regulated) and type III iodothyronine 5'-deiodinase (DIO3; down-regulated). DBDPE induced CYP1A4/5 29- and 59-fold at 0.2 muM in CEH and increased DIO1. None of the gene targets were responsive to BEHTBP exposure in CEH. The multi-tiered in vitro/in ovo screening approach was effective for assessing toxicological and molecular biological effects of these BFRs in an avian species. CI - Crown Copyright (c) 2011. Published by Elsevier Ireland Ltd. All rights reserved. FAU - Egloff, Caroline AU - Egloff C AD - Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, 20 Marie Curie Street, Ottawa, Ontario, Canada K1N6N5. FAU - Crump, Doug AU - Crump D FAU - Chiu, Suzanne AU - Chiu S FAU - Manning, Gillian AU - Manning G FAU - McLaren, Kristina K AU - McLaren KK FAU - Cassone, Cristina G AU - Cassone CG FAU - Letcher, Robert J AU - Letcher RJ FAU - Gauthier, Lewis T AU - Gauthier LT FAU - Kennedy, Sean W AU - Kennedy SW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110826 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Flame Retardants) RN - 0 (Polybrominated Biphenyls) RN - 0 (RNA, Messenger) RN - EC 1.11.1.- (iodothyronine deiodinase type I) RN - EC 1.11.1.8 (Iodide Peroxidase) RN - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases) RN - EC 1.14.14.1 (Cytochrome P450 Family 3) RN - EC 1.14.14.1 (cytochrome P-450 CYP3A37 (chicken)) SB - IM MH - Animals MH - Aryl Hydrocarbon Hydroxylases/biosynthesis/genetics MH - Cell Survival/drug effects MH - Chick Embryo MH - Cytochrome P450 Family 3 MH - Flame Retardants/*toxicity MH - Gene Expression Profiling MH - Gene Expression Regulation, Enzymologic/*drug effects MH - Hepatocytes/drug effects/metabolism MH - Iodide Peroxidase/biosynthesis/genetics MH - Liver/cytology/*drug effects/embryology/enzymology MH - Polybrominated Biphenyls/*toxicity MH - RNA, Messenger/*biosynthesis/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Statistics, Nonparametric EDAT- 2011/09/07 06:00 MHDA- 2012/01/19 06:00 CRDT- 2011/09/07 06:00 PHST- 2011/07/26 00:00 [received] PHST- 2011/08/18 00:00 [revised] PHST- 2011/08/19 00:00 [accepted] PHST- 2011/09/07 06:00 [entrez] PHST- 2011/09/07 06:00 [pubmed] PHST- 2012/01/19 06:00 [medline] AID - S0378-4274(11)01501-3 [pii] AID - 10.1016/j.toxlet.2011.08.015 [doi] PST - ppublish SO - Toxicol Lett. 2011 Nov 10;207(1):25-33. doi: 10.1016/j.toxlet.2011.08.015. Epub 2011 Aug 26.