Increased cytotoxicity of 2',2'-difluoro-2'-deoxycytidine in human leukemic cell-lines after a preincubation with cyclopentenyl cytosine.
Nucleosides Nucleotides Nucleic Acids
; 23(8-9): 1517-21, 2004 Oct.
Article
en En
| MEDLINE
| ID: mdl-15571289
The in vitro modulating effect of Cyclopentenyl cytosine (CPEC) on the metabolism of gemcitabine was studied in lymphocytic and myeloid leukemic cell-lines. In MOLT-3 cells, that were pretreated with CPEC, the incorporation of 2',2'-difluoro-2'-deoxycytidine triphosphate (dFdCTP) into DNA was significantly increased by 57-99% in comparison with cells that were only treated with gemcitabine. The increased incorporation of dFdCTP into DNA in CPEC pretreated cells was paralleled by an increase in apoptotic and necrotic cells of 17-34%. In HL-60 cells that were preincubated with CPEC, increased concentrations of the mono-/di- and triphosphate form of gemcitabine were observed, as well as an increased incorporation of dFdCTP into DNA (+773%). This increased incorporation was paralleled by a significant increase in apoptosis and necrosis. We conclude that CPEC enhances the incorporation of dFdCTP into DNA and thus increases the cytotoxicity of gemcitabine in lymphocytic and myeloid leukemic cell-lines.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Citidina
/
Desoxicitidina
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Nucleosides Nucleotides Nucleic Acids
Asunto de la revista:
BIOQUIMICA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Estados Unidos