Interaction between vitamin K3 and benzo(a)pyrene metabolism in uninduced microsomes.
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.
Byczkowski
J Z
JZ
Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.
Gessner
T
T
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014535:Uridine Diphosphate Glucuronic Acid / Q000494:pharmacology; D014812:Vitamin K / Q000494:pharmacology*
D008054:Lipid Peroxides; D013481:Superoxides; D014812:Vitamin K; D014535:Uridine Diphosphate Glucuronic Acid; D001564:Benzo(a)pyrene