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.
|
Authors | A Sato, J A Montgomery, J G Cory |
Journal | Cancer research
(Cancer Res)
Vol. 44
Issue 8
Pg. 3286-90
(Aug 1984)
ISSN: 0008-5472 [Print] United States |
PMID | 6611198
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Deoxyadenosines
- Pyrazoles
- Deoxycytidine
- Cytidine
- 2'-fluoro-2'-deoxyadenosine
- Vidarabine
- Deferoxamine
- 2,3-dihydro-1H-imidazo(1,2-b)pyrazole
- fludarabine
- Hydroxyurea
|
Topics |
- Animals
- Cell Survival
(drug effects)
- Cytidine
(metabolism)
- Deferoxamine
(toxicity)
- Deoxyadenosines
(analogs & derivatives, toxicity)
- Deoxycytidine
(biosynthesis)
- Drug Synergism
- Hydroxyurea
(toxicity)
- Kinetics
- Leukemia L1210
(physiopathology)
- Mice
- Pyrazoles
(toxicity)
- Vidarabine
(analogs & derivatives, toxicity)
|