This study was designed to clarify the mechanisms of action of selected antitumor agents of current or potential use in cancer chemotherapy. The metabolism and spontaneous degradation of dimethyltriazeno imidazole carboxamide (DIC, DTIC, Dacarbazine will be investigated with particular interest centered on: a) whether there is any correlation between the slow generation of 2-azahypoxanthine (the ultimate spontaneous degradation product of DIC) and therapeutic response, toxicity, or urinary excretion of AIC and b) the correlation between metabolic activation of DIC by endogenously supplied microsomes with cytotoxic activity toward Chinese hamster ovary cells (CHO) in vitro in the dark. The uptake and metabolism of inosine dialdehyde (Inox, IDA) will be investigated using appropriate CHO cell mutants and Inox which is labeled with 14C at the 8-position. Other related agents of interest may be included in the investigation. BIBLIOGRAPHIC REFERENCE: Saunders, P.P. and Chao, L.-Y.: Comparison of the actions of 5-Fluorouracil and Ftorafur in Escherichia coli. Antimicrobial Agents and Chemotherapy II, 451-454 (1977).
NIH ExPorter
NIH ExPorter