A comparison of free radical formation by quinone antitumour agents in MCF-7 cells and the role of NAD(P)H (quinone-acceptor) oxidoreductase (DT-diaphorase).

Electron paramagnetic resonance (EPR/ESR) spin trapping studies with DMPO revealed that purified rat liver NAD(P)H (quinone-acceptor) oxidoreductase (QAO) mediated hydroxyl radical formation by a diverse range of quinone-based antitumour agents. However, when MCF-7 S9 cell fraction was the source of QAO, EPR studies distinguished four different interactions by these agents and QAO with respect to hydroxyl radical formation: (i) hydroxyl radical formation by diaziquone (AZQ), menadione, 1AQ; 1,5AQ and 1,8AQ was mediated entirely or partially by QAO in MCF-7 S9 fraction; (ii) hydroxyl radical formation by daunorubicin and Adriamycin was not mediated by QAO in MCF-7 S9 fraction; (iii) hydroxyl radical formation by mitomycin C was stimulated in MCF-7 S9 fraction when QAO was inhibited by dicumarol; (iv) no hydroxyl radical formation was detected for 1,4AQ or mitoxantrone in MCF-7 S9 fraction. This study shows that purified rat liver QAO can mediate hydroxyl radical formation by a variety of diverse quinone antitumour agents. However, QAO did not necessarily contribute to hydroxyl radical formation by these agents in MCF-7 S9 fraction and in the case of mitomycin C, QAO played a protective role against hydroxyl radical formation.