title: In vitro and in ovo effects of four brominated flame retardants on toxicity and hepatic mRNA expression in chicken embryos.
abstract: 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 μM, egg injection: 0.1-10 μg/g nominal dose). In CEH, 10 μM 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 μM 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.
authors: Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, 20 Marie Curie Street, Ottawa, Ontario, Canada K1N6N5.
authors: Caroline
authors: C
authors: Egloff
authors: Doug
authors: D
authors: Crump
authors: Suzanne
authors: S
authors: Chiu
authors: Gillian
authors: G
authors: Manning
authors: Kristina K
authors: KK
authors: McLaren
authors: Cristina G
authors: CG
authors: Cassone
authors: Robert J
authors: RJ
authors: Letcher
authors: Lewis T
authors: LT
authors: Gauthier
authors: Sean W
authors: SW
authors: Kennedy
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D000072469:Cytochrome P450 Family 3; D005411:Flame Retardants / Q000633:toxicity*; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007453:Iodide Peroxidase / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D005411:Flame Retardants; D011075:Polybrominated Biphenyls; D012333:RNA, Messenger; C109812:iodothyronine deiodinase type I; D007453:Iodide Peroxidase; D001189:Aryl Hydrocarbon Hydroxylases; D000072469:Cytochrome P450 Family 3; C465259:cytochrome P-450 CYP3A37 (chicken)