Synergistic inhibition of leukemia L1210 cell growth in vitro by combinations of 2-fluoroadenine nucleosides and hydroxyurea or 2,3-dihydro-1H-pyrazole[2,3-a]imidazole.
Cancer Res
; 44(8): 3286-90, 1984 Aug.
Article
en En
| MEDLINE
| ID: mdl-6611198
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-A 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 microM) in combination with 2,3-dihydro-1H-pyrazole[2,3-a]imidazole gave synergistic inhibition of L1210 cell 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-pyrazole[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-pyrazole[2,3-a]imidazole or hydroxyurea gave strong synergistic inhibition of L1210 cell growth, even at the lowest concentration of 2-FdAdo (0.6 microM) studied. The presence of Desferal in the combination served to further potentiate the synergism.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Vidarabina
/
Leucemia L1210
/
Desoxiadenosinas
/
Hidroxiurea
Límite:
Animals
Idioma:
En
Revista:
Cancer Res
Año:
1984
Tipo del documento:
Article