A COMPARISON OF FREE-RADICAL FORMATION BY QUINONE ANTITUMOR AGENTS INMCF-7 CELLS AND THE ROLE OF NAD(P)H (QUINONE-ACCEPTOR) OXIDOREDUCTASE(DT-DIAPHORASE)

Electron paramagnetic resonance (EPR/ESR) spin trapping studies with D MPO revealed that purified rat liver NAD(P)H (quinone-acceptor) oxidor eductase (QAO) mediated hydroxyl radical formation by a diverse range of quinone-based antitumour agents. However, when MCF-7 S9 cell fracti on was the source of QAO, EPR studies distinguished four different int eractions by these agents and QAO with respect to hydroxyl radical for mation: (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 Ad riamycin was not mediated by QAO in MCF-7 S9 fraction; (iii) hydroxyl radical formation by mitomycin C was stimulated in MCF-7 S9 fraction w hen QAO was inhibited by dicumarol; (iv) no hydroxyl radical formation was detected for 1,4AQ or mitoxantrone in MCF-7 S9 fraction. This stu dy shows that purified rat liver QAO can mediate hydroxyl radical form ation 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.