title: Effects of co-exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and perfluorooctane sulfonate or perfluorooctanoic acid on expression of cytochrome P450 isoforms in chicken (Gallus gallus) embryo hepatocyte cultures.
abstract: In this study we investigated the effect of a single-compound exposure or two compound co-exposure to tetrachlorodibenzo-p-dioxin (TCDD) plus perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) on the mRNA expression of cytochromes P450 (CYP) 1A4, 4V2 and 3A37, ethoxyresorufin-O-deethylase (EROD) activity and cell viability in chicken (Gallus gallus domesticus) embryo primary hepatocyte cultures. Cell viability after 24 h of incubation was significantly decreased in cells exposed to PFOS at concentrations between 30 microM and 60 microM with or without co-exposure to TCDD (0.3 nM at maximum). PFOA did not decrease cell viability even at maximum concentrations of 60 microM. TCDD induced CYP1A4 mRNA and EROD activity substantially as reported previously. PFOS also increased CYP1A4 mRNA in a concentration-dependent manner. Co-exposure of cells to PFOS plus TCDD did not change CYP1A4 mRNA levels compared to cells treated with TCDD alone. PFOS alone did not induce CYP4V2 mRNA, however 40-50 microM PFOS plus TCDD (0.3 nM) induced CYP4V2 mRNA compared to TCDD alone (P<0.05). This trend was similar to that observed with co-exposure to TCDD plus PFOA, suggesting that PFOA alone did not induce CYP4V2 mRNA, whereas co-exposure to TCDD plus PFOA induced the expression levels. PFOS alone decreased CYP3A37 mRNA by a maximum of 45%, however after co-exposure to TCDD, recovery of mRNA expression to levels measured in DMSO-treated cells was observed. Our data suggest a complex gene response to mixtures of dioxin-like and perfluorinated compounds.
authors.affiliation: National Wildlife Research Centre, Environment Canada, Carleton University, Ottawa, ON, Canada.
authors.forename: Michio X
authors.initials: MX
authors.lastname: Watanabe
authors.forename: Stephanie P
authors.initials: SP
authors.lastname: Jones
authors.forename: Hisato
authors.initials: H
authors.lastname: Iwata
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
mesh_terms: D017738:Alkanesulfonic Acids / Q000494:pharmacology*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D030161:Avian Proteins / Q000096:biosynthesis; D002210:Caprylates / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D000072469:Cytochrome P450 Family 3; D004790:Enzyme Induction; D005466:Fluorocarbons / Q000494:pharmacology*; D022781:Hepatocytes / Q000201:enzymology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D017738:Alkanesulfonic Acids; D030161:Avian Proteins; D002210:Caprylates; D005466:Fluorocarbons; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid; D001189:Aryl Hydrocarbon Hydroxylases; C416342:CYP1A4 protein, Gallus gallus; D019363:Cytochrome P-450 CYP1A1; D000072469:Cytochrome P450 Family 3; C465259:cytochrome P-450 CYP3A37 (chicken)