CONVERSION OF 4-NITROQUINOLINE 1-OXIDE (4NQO) TO 4-HYDROXYAMINOQUINOLINE 1-OXIDE BY A DICUMAROL-RESISTANT HEPATIC-4NQO NITROREDUCATASE IN RATS AND MICE

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.