ISSN:
1573-7373
Keywords:
glioma cell
;
bacterial cytosine deaminase
;
5-fluorocytosine
;
interferon
;
apoptosis
;
DNA damage
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract To explore the antitumor mechanism of bacterial cytosine deaminase plus 5-fluorocytosine (CD/5-FCyt) in combination with interferons (IFNs), glioma cells were transduced with recombinant retroviruses expressing CD. The transduced glioma cells become sensitive to the nontoxic prodrug 5-FCyt. Apoptosis, DNA damage, bystander effect, and inhibition of thymidylate synthase (TS) and DNA synthesis are associated with CD/5-FCyt-mediated glioma cell killing. Furthermore, IFNs enhance this effect by increasing DNA damage and further inhibiting TS activity. The bystander effect is mediated by the release of cytotoxic metabolites of 5-FCyt into the extracellular milieu triggering apoptosis and DNA damage. Our data indicate that the use of CD/5-FCyt in combination with IFNs may provide a more effective approach for the treatment of brain tumors.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1005883128175
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