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.