title: Exposure to 3,3',4,4',5-pentachlorobiphenyl during embryonic development has a minimal effect on the cytochrome P4501A response to 2,3,7,8-tetrachlorodibenzo-p-dioxin in cultured chicken embryo hepatocytes.
abstract: Concentrations of dioxin-like compounds in avian eggs can vary substantially between individuals, species, and collection sites. Although the inducibility of cytochrome P4501A (CYPIA) in hepatocyte cultures is commonly used to predict species sensitivity to environmental contaminants, it is not known how exposure to dioxin-like compounds during embryonic development might alter this biomarker response. To investigate this question, we injected vehicle or 0.4, 0.8, or 1.6 microg/kg of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) into the air cell of fertilized chicken eggs before incubation, and we measured CYP1A endpoints in cultured hepatocytes of day-19 embryos from each treatment group. The CYP1A response to PCB 126 also was assessed in whole liver tissue. Embryonic exposure to the most environmentally relevant treatment, 0.4 microg/kg of PCB 126, increased CYPIA4 mRNA expression 29-fold compared to control values in whole liver tissue but only twofold compared to control values in cultured hepatocytes. The CYPIA response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was not altered in hepatocytes cultured from embryos treated with 0.4 microg/kg of PCB 126, but at 0.8 and 1.6 microg/kg of PCB 126, several concentration-dependent effects were observed. For example, embryos exposed to higher concentrations of PCB 126 in ovo were more responsive to CYP1A mRNA induction by TCDD in vitro. These findings suggest that exposure to environmental levels of dioxin-like compounds during incubation is not likely to alter species-sensitivity estimates derived from in vitro CYP1A data.
authors.affiliation: Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Head
authors.forename: Jason
authors.initials: J
authors.lastname: O'Brien
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000201:enzymology / Q000473:pathology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C023035:3,4,5,3',4'-pentachlorobiphenyl