Conversion of 4-nitroquinoline 1-oxide (4NQO) to 4-hydroxyaminoquinoline 1-oxide by a dicumarol-resistant hepatic 4NQO nitroreductase in rats and mice

Biochem Pharmacol. 1993 Oct 5;46(7):1217-21. doi: 10.1016/0006-2952(93)90470-h.

Abstract

The product formed from 4-nitroquinoline 1-oxide (4NQO), a potent carcinogen, by the action of mouse NADH:4NQO nitroreductase NR-1 was directly identified as 4-hydroxyaminoquinoline 1-oxide (4HAQO) by high performance liquid chromatography analyses in two systems. In liver cytosols from both male and female mice, NADH:4NQO nitroreductase was the predominant enzyme catalyzing the reduction of 4NQO. Rat liver cytosol catalyzed the conversion of 4NQO to either 4HAQO or a glutathione conjugate depending upon coenzyme or cosubstrate availability. Whereas NAD(P)H:quinone reductase (NAD(P)H:(quinone acceptor) oxidoreductase; DT diaphorase; EC 1.6.99.2) was the predominant 4NQO reductase present in liver cytosol from Sprague-Dawley rats, dicumarol-resistant NADH:4NQO nitroreductase specific activities were comparable with those of mouse liver cytosols. A 4NQO nitroreductase from rat liver cytosol was separated from NAD(P)H:quinone reductase chromatographically and shown to have a strong preference for NADH and to be insensitive to inhibition by dicumarol.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Hydroxyaminoquinoline-1-oxide / metabolism*
  • 4-Nitroquinoline-1-oxide / metabolism*
  • Amino Acid Sequence
  • Animals
  • Chromatography, High Pressure Liquid
  • Cytosol / enzymology
  • Female
  • Liver / enzymology*
  • Male
  • Mice
  • Molecular Sequence Data
  • NADH, NADPH Oxidoreductases / isolation & purification
  • NADH, NADPH Oxidoreductases / metabolism*
  • NADP / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • 4-Hydroxyaminoquinoline-1-oxide
  • NADP
  • 4-Nitroquinoline-1-oxide
  • NADH, NADPH Oxidoreductases
  • nitroquinoline N-oxide reductase