ACTIVATION OF THE ANTITUMOR QUINONE AZQ BY DT-DIAPHORASE

dt -二磷酸腺苷酶，虽然通常被认为是一种保护酶

DT-diaphorase, although generally considered to be a protective enzyme against quinone-induced toxicity, has been suggested to play a role in the bioactivation of antitumor quinones. The precise role of DT-diaphorase in bioreductive activation of quinones remains controversial. We propose to utilize DT-diaphorase purified from HT-29 human colon carcinoma cells to examine the role of this enzyme in bioactive of AZQ* and Mitomycin C. Whether AZQ, Mitomycin C and their analogs are substrates for HT-29 DT- diaphorase and whether metabolism by this enzyme results in the production of metabolites which can induce damage to cellular macromolecules (DNA, proteins, soluble thiols) will be examined. Studies in cellular systems will also be performed to identify intracellular targets of antitumor quinones. These studies will allow unequivocal confirmation of the role of DT- diaphorase in bioreductive activation of AZQ and Mitomycin C in human tumor cells. * AZQ - Diaziquone-(2,5-bis(1-aziridinyl)-3,0-bis-(carboethoxyamino)1,4- benzoquinone.