5-Fluorocytosine-mediated apoptosis and DNA damage in glioma cells engineered to express cytosine deaminase and their enhancement with interferon

Zhao Hui Wang, Stanley Samuels, Miguel A. Gama Sosa, Edwin H. Kolodny

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish
Pages (from-to)219-229
Number of pages11
JournalJournal of Neuro-Oncology
Volume36
Issue number3
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • 5-fluorocytosine
  • Apoptosis
  • Bacterial cytosine deaminase
  • DNA damage
  • Glioma cell
  • Interferon

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