Characterization of xenobiotic metabolism in the feral teleost northern pike (Esox lucius)

Sammanfattning: A basic characterization of xenobiotic metabolism in the feral teleost Northern pike has been performed. The different aspects of concern have been:a) investigation of the uptake and distribution to different body compartments of the carcinogen and environmental pollutant benzo(a)pyrene using whole-body autoradiography and scintillation counting. Using environmentally observed concentrations of benzo(a)pyrene in the water uptake was found to be rapid, and the bioconcentration factor was from about 50 (in many organs) to about 80,000 (in the bile). About 90% of the total uptake in the pike was found in the liver-bile- intestine and gills - blood - head kidney - trunk kidney - urine systems, indicating the importance of these systems in uptake, metabolism and excretion.b) formation of mutagenic metabolites from benzo(a)pyrene and 2-aminoanthracene by the S-9 fraction from the liver of untreated and 3-methylcholanthrene-treated Northern pike and its correlation with benzo(a)pyrene monooxygenase activity. The strong correlation between revertant number and this cytochrome P-450-catalyzed activity indicates that the major factor in the production of reactive intermediates in this system is the phase I cytochrome P-450 system.c) initial .in vitro characterization of xenobiotic metabolism in the pike liver. These studies revealed that this species is well-suited for this type of investigation. Similarities with the corresponding systems in mammals were observed, but also striking differences, e.g., notably lack of induction with phénobarbital.d) preparation and characterization of subcellular fractions from the gills, head kidney, trunk kidney, liver and intestine. The supernatant and microsomal fractions were relativity pure, so that comparisons between different tissues and organs of the Northern pike, as well as with literature data on mammals, can be performed.e) further iji vitro characterization of the enzymes involved in xenobiotic metabolism in the gills , head kidney, trunk kidney, liver and intestine. These investigations confirm our earlier conclusion about the usefulness of subfractions from the liver and extrahepatic tissues of Northern pike for such characterization. Our preliminary data indicate that in vitro activities of enzymes involved in the metabolism of xenobiotics are not generally lower in Northern pike compared to mammals, nor did the liver exhibit the highest activity for all enzymes examined.