Interaction between vitamin K3 and benzo(a)pyrene metabolism in uninduced microsomes. 1987

J Z Byczkowski, and T Gessner
Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.

1. Relationship between quinone recycling, glucuronidation and benzo(a)pyrene (BaP) oxygenation was investigated in uninduced mouse liver microsomes--native and modified by Fe3+.FeEDTA and/or superoxide (O2-.)-initiated lipid peroxidation. 2. A functional coupling between glucuronidation of reduced quinones and BaP metabolism, not discernible during BaP metabolism by native uninduced microsomes, was demonstrable in the presence of a model quinone, vitamin K3 (menadione). 3. Menadione inhibited BaP oxygenation in microsomal preparations, by siphoning off electrons from cytochrome P-450, while addition of UDPGA reversed this effect by glucuronidation of menadiol. 4. Fe3+.FeEDTA and/or O2-.-initiated lipid peroxidation decreased, to different extent, the microsomal enzymatic activities involved in quinone metabolism. The most sensitive was quinone reductase activity, which was reduced by 77%. Under peroxidative conditions menadione was a less effective inhibitor of BaP metabolism. 5. The important role of the balance between quinone reductase and UDP-glucuronyltransferase activities in the coupling with BaP oxygenation is discussed. A mechanism by which vitamin K3 could exert a regulatory effect on BaP metabolism is proposed.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008054 Lipid Peroxides Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. Fatty Acid Hydroperoxide,Lipid Peroxide,Lipoperoxide,Fatty Acid Hydroperoxides,Lipid Hydroperoxide,Lipoperoxides,Acid Hydroperoxide, Fatty,Acid Hydroperoxides, Fatty,Hydroperoxide, Fatty Acid,Hydroperoxide, Lipid,Hydroperoxides, Fatty Acid,Peroxide, Lipid,Peroxides, Lipid
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001564 Benzo(a)pyrene A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. 3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene
D013481 Superoxides Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides. Superoxide Radical,Superoxide,Superoxide Anion
D014535 Uridine Diphosphate Glucuronic Acid A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones. UDP Glucuronic Acid,UDPGA,Uridine Diphosphoglucuronic Acid,Acid, UDP Glucuronic,Acid, Uridine Diphosphoglucuronic,Diphosphoglucuronic Acid, Uridine,Glucuronic Acid, UDP
D014812 Vitamin K A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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