Modulation of Arabinosyladenine Metabolism by 2′-Deoxycoformycin in the Therapy of Human Acute Leukemia
Arabinosyladenine (araA) is a functional analog of deoxy-adenosine that exhibits antiviral activity but only weak antitumor activity in humans. The therapeutic efficacy of araA against human malignancies is known to be limited by its deamination to arabinosylhypoxanthine by adenosine deaminase. Although the likelihood of increasing the activity of araA after inhibition of adenosine deaminase had been speculated upon, it was not until potent adenosine deaminase inhibitors such as 2′-deoxyco-formycin (dCF) became available that the potential for such combination chemotherapy could be evaluated. It is now well established that both the toxicity to cells in culture and therapeutic activity of araA in tumor-bearing mice are increased by coadministration with pharmacologically active, but otherwise nontoxic doses of a deaminase inhibitor (1–3)
KeywordsLeukemic Cell Adenosine Deaminase Cellular Concentration Bolus Infusion Functional Analog
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