The metabolism of 4-nitroquinoline-1-oxide, a carcinogen. 3. An enzyme catalyzing the conversion of 4-nitroquinoline-1-oxide to 4-hydroxyaminoquinoline-1-oxide in rat liver and hepatomas.

Abstract

Summary The activity of an enzyme that converts 4-nitroquinoline-1-oxide, a carcinogen, to 4-hydroxyaminoquinoline-1-oxide, a possible proximate carcinogen of 4-nitroquinoline-1-oxide, was assayed in extracts of normal liver and in a variety of slowly and fast growing hepatomas. Normal liver and slowly growing hepatomas contained relatively large amounts of this enzyme, while fast growing hepatomas apparently lacked it. The enzyme, which converts 4-nitroquinoline-1-oxide to 4-hydroxyaminoquinoline-1-oxide, was purified 80-fold from rat liver supernatant. NADH2 or NADPH2 served as hydrogen donors, and 4-nitroquinoline-1-oxide, 4-nitro-6-quinolinecarboxylic acid-1-oxide, and dichlorophenolindophenol could act as hydrogen acceptors. The enzyme activity was inhibited by dicoumarol, and stimulated by albumin and Tween 80. The enzyme was identified as DT diaphorase. The role of this enzyme in carcinogenesis by 4NQO is discussed.