The role of NAD(P)H oxidoreductase (DT-diaphorase) in the bioactivation ofquinone-containing antitumor agents: A review

Bioactivation of quinone-containing anticancer agents has been studied exte nsively within the context of the chemistry and structure of the individual quinones which may result in various mechanisms of bioactivation and activ ity. In this review we focus on the two electron enzymatic reduction/activa tion of quinone-containing anticancer agents by DT Diaphorase (DTD). This e nzyme has become important in oncopharmacology because its activity varies with tissues and it has been found to be elevated in tumors. Thus, a select ive tumor cell kill can exist for agents that are good substrates for this enzyme. In addition, the enzyme can be induced by a variety of agents, a fa ct that can be used in chemotherapy. That is induction by a nontoxic agent followed by treatment with a good DT-Diaphorase substrate. A wide variety o f anticancer drugs are discussed some of which are not good substrates such as Adriamycin, and some of which are excellent substrates. The latter cate gory includes a variety of quinone containing alkylating agents. (C) 2000 E lsevier Science Inc.