Induction of CYP1A in primary cultures of rainbow trout (Oncorhynchus mykiss) liver cells: concentration-response relationships of four model substances.
The study aims to evaluate short-term teleost hepatocyte cultures to establish dose-response curves for CYP1A induction and to rank the relative potencies of xenobiotics. Hepatocytes isolated from rainbow trout (Oncorhynchus mykiss) were incubated in vitro in coculture with RTG-2 cells in serum-free, chemically defined medium. Concentration-dependent induction of cytochrome P4501A was observed after treatment of the hepatocytes for 48 h with one of the four polyaromatic hydrocarbons: 3-methylcholanthrene, benzo[a]pyrene, benz[a]anthracene, and beta-naphthoflavone. The induction response was assessed by measuring 7-ethoxyresorufin-O-deethylase (EROD) and 7-ethoxycoumarin-O-deethylase (ECOD). From the data, EC50 and maximal induction response values were calculated. The rank order of EC50 values differed among the four model compounds, depending on the endpoint parameter. EC50 values for EROD and ECOD also differed in comparison to published affinity data for mammalian arylhydrocarbon receptor. The results of this study indicate the potential of primary teleostean hepatocyte cultures for studies on induction potency and regulation of piscine cytochrome P4501A. A drawback, however, appears to be the pronounced interindividual variation of the quantitative response of the cells.
Scholz
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S
Department of Chemical Ecotoxicology, UFZ Centre of Environmental Research, Permoser Str. 15, Leipzig, D-04318, Germany. scholz_s@rcs.urz.tu-dresden.de
Segner
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H
D000818:Animals; D002384:Catalysis; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000201:enzymology*; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013329:Structure-Activity Relationship
D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1