MODULATION OF 9-BETA-D-ARABINOFURANOSYLADENINE 5'-TRIPHOSPHATE AND DEOXYADENOSINE TRIPHOSPHATE IN LEUKEMIC-CELLS BY 2'-DEOXYCOFORMYCIN DURING THERAPY WITH 9-BETA-D-ARABINOFURANOSYLADENINE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (5) , 2092-2096
Abstract
The effect of the adenosine deaminase inhibitor, 2''-deoxycoformycin, on cellular nucleotides during therapy with continuous infusion of 9-.beta.-D-arabinofuranosyladenine (ara-A) was investigated. In 3 courses of treatment using increasing doses, the active 5''-triphosphate (ara-ATP), accumulated in leukemic cells and erythrocytes from a patient treated for acute lymphocytic leukemia in proportion to the dose of ara-A. The cellular ara-ATP concentration increased more than 5-fold after the injection of a single, nontoxic, but pharmacologically active dose of 2''-deoxycoformycin 24 h after initiation of ara-A infusion. This reponse was associated with a concomitant increase in the cellular deoxyadenosine triphosphate concentrations to levels equal to or greater than those of ara-ATP throughout the 3 treatment courses studied. A competitive relationship exists between deoxyadenosine triphosphate and ara-ATP for the inhibition of DNA synthesis in cultured human lymphoblastoid cells; the ratio of the cellular concentrations of these nucleotides could predict the extent of inhibition of DNA synthesis. Administration of 2''-deoxycoformycin may create a cellular biochemical milieu that could be antagonistic to the inhibition of DNA synthesis by ara-ATP.