SYNERGISTIC INHIBITION OF LEUKEMIA-L1210 CELL-GROWTH INVITRO BY COMBINATIONS OF 2-FLUOROADENINE NUCLEOSIDES AND HYDROXYUREA OR 2,3-DIHYDRO-1H-PYRAZOLE[2,3-A]IMIDAZOLE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (8) , 3286-3290
Abstract
9-.beta.-D-Arabinofuranosyl-2-fluoroadenine (2-F-ara-A) and 2-fluoro-2''-deoxyadenosine (2-FdAdo) were potent inhibitors of L1210 cell growth in culture. Even though these 2-fluoroadenine nucleosides are very poor substrates for adenosine deaminase, erythro-9-(2-hydroxyl-3-nonyl)adenine potentiated the growth-inhibitory properties of 2-FdAdo, but not 2-F-ara-A, in a synergistic manner. 2-FdAdo and 2-F-ara-F inhibited the conversion of [3H]cytidine to deoxycytidine nucleotides and incorporation into DNA, suggesting that ribonucleotide reductase was an intracellular site of action. 2-F-ara-A (6 .mu.M) in combination with 2,3-dihydro-1H-pyrazolo[2,3-a]imidazole gave synergistic inhibition of L1210 cells growth. At lower concentrations of 2-F-ara-A, the inhibition by this combination was only additive. The addition of Desferal to the combination of 2-F-ara-A plus 2,3-dihydro-1H-pyrazolo[2,3-a]imidazole provided a strong synergistic combination. Similar results were obtained with combinations which included F-ara-A, hydroxyurea and Desferal. The combinations of 2-FdAdo plus 2,3-dihydro-1H-pyrazolol[2,3-a]imidazole or hydroxyurea gave strong synergistic inhibition of L1210 cell growth, even at the lowest concentration of 2-FdAdo (0.6 .mu.M) studied. The presence of Desferal in the combination served to further potentiate the synergism.