The quinone-containing anticaner agents, including the anthracyclines and mitomycin C play an important role in the treatment of a wide variety of human malignancies. Recent studies indicate that these drugs may be converted to free radical intermediates in vivo which could explain, in part, their antitumor and cardiotoxic properties. We propose to examine sites of drug-enhanced reactive oxygen metabolism in the heart and in experimental tumor systems, and the enzymatic mechanisms responsible for producing these species. We have developed model systems in which the cardiotoxic properties of the anthracyclines can be blocked by enhancing endogenous tissue defenses against free radicals. Hence, we also propose to investigate the effect of free radical scavenging agents on drug-induced oxygen radical formation and the antineoplastic activity of these quinones.
