Menadione inhibition of benzo(a)pyrene metabolism in whole cells, microsomes and reconstituted systems |
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Authors: | I J Sadowski J A Wright D Ollmann L G Israels |
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Abstract: | Menadione is known to decrease the mixed function oxidase mediated metabolism of a number of substrates in microsomal systems. The present study examines the effect of menadione on benzo(a)pyrene metabolism in whole cells, microsomes and a semi-purified reconstituted mixed function oxidase system. Menadione has a high affinity for the NADPH dependent cytochrome P-450 reductase and acts as a competitive inhibitor of cytochrome P-450 reductase in the metabolism of benzo(a)pyrene. This is the mechanism of inhibition of aryl hydrocarbon hydroxylase by menadione in reconstituted systems. In a whole cell system and at low concentrations of menadione, depletion of reduced pyridine nucleotides is the initial inhibitory event. |
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