One-electron reduction of mitomycin c by rat liver: role of cytochrome P-450 and NADPH-cytochrome P-450 reductase

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
R M VromansN P Vermeulen

Abstract

1. The role of cytochrome P-450 in the one-electron reduction of mitomycin c was studied in rat hepatic microsomal systems and in reconstituted systems of purified cytochrome P-450. Formation of H2O2 from redox cycling of the reduced mitomycin c in the presence of O2 and the alkylation of p-nitrobenzylpyridine (NBP) in the absence of O2 were taken as parameters. 2. With liver microsomes from both 3-methylcholanthrene (MC)- and phenobarbital (PB)-pretreated rats, reverse type I difference spectra were observed, indicative of a weak interaction between mitomycin c and the substrate binding site of cytochrome P-450. Mitomycin c inhibited the oxidative dealkylation of aminopyrine and ethoxyresorufin in both microsomal systems. 3. Under aerobic conditions the H2O2 production in the microsomal systems was dependent on NADPH, O2 and mitomycin c, and was inhibited by the cytochrome P-450 inhibitors, metyrapone and SKF-525A. 4. Although purified NADPH-cytochrome P-450 reductase was also effective in reduction of mitomycin c and the concomitant reduction of O2, complete microsomal systems and fully reconstituted systems of cytochrome P-450b or P-450c and the reductase were much more efficient. 5. Under anaerobic conditions in the microso...Continue Reading

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Citations

Nov 20, 1998·Pharmacology & Toxicology·K FurunoN Sugihara
May 27, 2010·Molecular Cancer Therapeutics·Yun WangJeffrey D Laskin
Nov 26, 2002·International Journal of Cancer. Journal International Du Cancer·Octávia Monteiro GilJosé Rueff
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Aug 30, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Haydar Celik, Emel Arinç
Sep 21, 2011·Veterinary Ophthalmology·Rangan GuptaRajiv R Mohan

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