title: Induction and inhibition of cytochrome P450-catalysed reduction of biologically active benfluron N-oxide.
abstract: Benfluron N-oxide [5-(2-N-oxo-2-N,N'-dimethylaminoethoxy)-7-oxo-7-H-benzo[c]fluorene] is a biologically active substance which displays a cytostatic effect on several experimental tumour cells. The main metabolic pathway of benfluron N-oxide in vitro and in vitro--its reduction to the parent tertiary amine benfluron--and the role of cytochrome P450 in this reduction were studied. The value of the benfluron N-oxide/benfluron redox potential as a criterion of suitability of the substrate for cytochrome P450 reductase activity was determined. Results of induction and inhibition studies on rats suggest that cytochromes P4502B and P4502E1 participate in microsomal reduction of benfluron N-oxide. Unlike most cytochrome P450 catalysed reactions, the reduction of benfluron N-oxide also occurs under aerobic conditions. Microsomes induced by phenobarbital, ethanol or beta-naphthoflavone showed no significantly greater inhibitory effect of oxygen on benfluron N-oxide reduction.
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Skálová
authors.forename: M
authors.initials: M
authors.lastname: Nobilis
authors.forename: B
authors.initials: B
authors.lastname: Szotáková
authors.forename: V
authors.initials: V
authors.lastname: Wsól
authors.forename: E
authors.initials: E
authors.lastname: Kvasnicková
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002384:Catalysis; D019392:Cytochrome P-450 CYP2E1 / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D005449:Fluorenes / Q000493:pharmacokinetics*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D005449:Fluorenes; C034234:VUFB 13468; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase