title: Single and mixture effects of aquatic micropollutants studied in precision-cut liver slices of Atlantic cod (Gadus morhua).
abstract: The low concentrations of most contaminants in the aquatic environment individually may not affect the normal function of the organisms on their own. However, when combined, complex mixtures may provoke unexpected effects even at low amounts. Selected aquatic micropollutants such as chlorpyrifos, bis-(2-ethylhexyl)-phthalate (DEHP), perfluorooctanoic acid (PFOA) and 17α-ethinylestradiol (EE2) were tested singly and in mixtures at nM to μM concentrations using precision-cut liver slices (PCLS) of Atlantic cod (Gadus morhua). Fish liver is a target organ for contaminants due to its crucial role in detoxification processes. In order to understand the effects on distinct key liver metabolic pathways, transcription levels of various genes were measured, including cyp1a1 and cyp3a, involved in the metabolism of organic compounds, including toxic ones, and the catabolism of bile acids and steroid hormones; cyp7a1, fabp and hmg-CoA, involved in lipid and cholesterol homeostasis; cyp24a1, involved in vitamin D metabolism; and vtg, a key gene in xenoestrogenic response. Only EE2 had significant effects on gene expression in cod liver slices when exposed singly at the concentrations tested. However, when exposed in combinations, effects not detected in single exposure conditions arose, suggesting complex interactions between studied pollutants that could not be predicted from the results of individual exposure scenarios. Thus, the present work highlights the importance of assessing mixtures when describing the toxic effects of micropollutants to fish liver metabolism.
authors.affiliation: Dept. Zoology and Cell Biology, Faculty of Science and Technology and Research Centre for Experimental Marine Biology and Biotechnology (PIE), University of the Basque Country (UPV/EHU), Basque Country Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bizarro
authors.affiliation: Dept. of Biology, University of Bergen, N-5020 Bergen, Norway.
authors.forename: Marta
authors.initials: M
authors.lastname: Eide
authors.affiliation: Dept. of Biology, University of Bergen, N-5020 Bergen, Norway; Dept.of Biosciences, University of Oslo, N-0316 Oslo, Norway.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hitchcock
authors.affiliation: Dept. of Biology, University of Bergen, N-5020 Bergen, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Goksøyr
authors.affiliation: Dept. Zoology and Cell Biology, Faculty of Science and Technology and Research Centre for Experimental Marine Biology and Biotechnology (PIE), University of the Basque Country (UPV/EHU), Basque Country Spain. Electronic address: maren.ortiz@ehu.eus.
authors.forename: Maren
authors.initials: M
authors.lastname: Ortiz-Zarragoitia
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002210:Caprylates / Q000378:metabolism / Q000633:toxicity*; D004390:Chlorpyrifos / Q000378:metabolism / Q000633:toxicity*; D004051:Diethylhexyl Phthalate / Q000378:metabolism / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000378:metabolism / Q000633:toxicity*; D005466:Fluorocarbons / Q000378:metabolism / Q000633:toxicity*; D048389:Gadus morhua / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D002210:Caprylates; D005466:Fluorocarbons; D014874:Water Pollutants, Chemical; D004997:Ethinyl Estradiol; C023036:perfluorooctanoic acid; D004051:Diethylhexyl Phthalate; D004390:Chlorpyrifos
keywords: Cod; Contaminant mixtures; Emerging pollutants; Liver metabolism; Precision-cut liver slices