Metabolism of 2,2′,5,5′-tetrachlorobiphenyl: Formation of mono- and bis-methyl sulphone metabolites with a selective affinity for the lung and kidney tissues in mice
Metabolism of 2,4′,5-trichlorobiphenyl: Role of the intestinal microflora in the formation of bronchial-seeking methyl sulphone metabolites in mice
Metabolism of 2,4′,5-trichlorobiphenyl by the mercapturic acid pathway
Preparation and characterization of subcellular fractions from the liver of the northern pike, Esox lucius
The present study was designed to prepare and characterize subcellular fractions from the liver of the Northern pike (Esox lucius), with special emphasis on the preparation of microsomal fractions suitable for studying xenobiotic metabolism. The purity of the different fractions obtained by differential centrifugation, as well as the recovery of different organelles, was determined using both enzyme markers and morphological examination with the electron microscope. Attempts were also made to increase the recovery of fragments of the endoplasmic reticulum in the microsomal fraction. Finally, the subcellular distribution of several drug-metabolizing enzymes (cytochrome P-450, benzpyrene monooxygenase, epoxide hydrolase and glutathione transferases) were determined. With the exception of the subcellular distribution of epoxide hydrolase, the results obtained here resemble closely those reported for rat liver and the microsomal fraction prepared is highly suitable for further studies of drug metabolism in pike liver.
Effect of phthalate ester metabolites on rat liver
Metabolism of 2,4′,5-trichlorobiphenyl: Enrichment of hydroxylated and methyl sulphone metabolites in the uterine luminal fluid of pregnant mice
Formation of mutagenic metabolites from benzo(a)pyrene and 2-aminoanthracene by the S-9 fraction from the liver of the Northern pike (Esox lucius): Inducibility with 3-methylcholanthrene and correlation with benzo[a]pyrene monooxygenase activity
The mutagenicity of benzo[a]pyrene and 2-aminoanthracene in the Ames test using the S-9 fraction from the liver of the Northern pike (Esox lucius) was tested. S-9 fractions were prepared both from fish injected intraperitoneally with 3-methylcholanthrene and from control animals. In addition benzo[a]pyrene monooxygenase activity was assayed in the same S-9 fractions used in the Ames test.
S-9 fractions from the liver of the Northern pike were found to convert benzo[a]pyrene and 2-aminoanthracene to mutagenic metabolites. The number of revertants obtained was increased 2–4-fold in the case of 2-aminoanthracene and 3–14-fold in the case of benzo[a]pyrene by pretreatment of the pike with a single intraperitoneal injection of 3-methylcholanthrene. This injection also caused a 2–6-fold increase in the benzo[a]pyrene monooxygenase activity of the S-9 fractions used. These increases in mutagenicity and activity occur mainly during the first 4–12 days after the injection, but further small increases are observed for as long as 60 days.
A strong positive correlation was found between the benzo[a]pyrene monooxygenase activity of the S-9 fractions used and their ability to give rise to revertants in the Ames test using 2-aminoanthracene or benzo[a]pyrene. This indicates that the major determining factor in the production of reactive metabolites which attack DNA in this in vitro system is the activity of the phase I cytochrome P-450 system.