DT-diaphorase: possible roles in cancer chemotherapy and carcinogenesis

DT-diaphorase [also called NAD(P)H:menadione oxidoreductase; NAD(P)H:(quinone acceptor) oxidoreductase; quinone reductase, azo-dye reductase] (EC.1.6.99.2) has been shown to have a role in activation of quinone-containing cancer chemotherapeutic prodrugs to their active form, as well as inactivation of a variety of xenobiotics involved in carcinogenesis. To illustrate the basis of this dichotomy, a brief review of the historical and recent background of studies on DT-diaphorase is given. Recent data from the laboratory of the authors on the nature of the protein coded for by a recently identified human polymorphism, a C to T transition at nucleotide 609 of DT-diaphorase cDNA, and the frequency of this mutation in anal canal carcinoma patients is presented. Finally, a series of questions about the role of DT-diaphorase in both normal and malignant cells is raised based on the results of others that have been published in the last 2-3 years.