Effect of inhibitors of the FAD-containing monooxygenase system from rat liver microsomes on monomethylhydrazine metabolism and activation to reactive metabolites

Arch Toxicol. 1986 May;59(1):64-6. doi: 10.1007/BF00263961.

Abstract

Several inhibitors of the FAD-containing monooxygenase (FAD-MO) system from rat liver microsomes (imipramine, chlorpromazine, mercaptoethylamine, dithiothreitol, naphthylthiourea, phenylthiocarbamide) and one inhibitor of the liver microsomal cytochrome P-450 (P-450)-mediated biotransformations (SKF 525 A), were tested as possible inhibitors of monomethylhydrazine (MMH) biotransformation to CO2 and to reactive metabolites that bind covalently to nucleic acids and proteins. Results confirm previous suggestions that both FAD-MO and P-450 are involved in MMH metabolism to CO2 and suggest a similar participation of both systems for production of reactive metabolites interacting with macromolecules.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biotransformation / drug effects
  • Cytochrome P-450 Enzyme System / metabolism
  • Flavin-Adenine Dinucleotide / metabolism*
  • Male
  • Methylhydrazines / metabolism*
  • Microsomes, Liver / enzymology*
  • Mixed Function Oxygenases / antagonists & inhibitors*
  • Rats
  • Rats, Inbred Strains

Substances

  • Methylhydrazines
  • Flavin-Adenine Dinucleotide
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases