PMID: 9524100Apr 2, 1998Paper

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

Journal of Neuro-oncology
Z H WangE H Kolodny

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.

Citations

Jul 23, 2020·Frontiers in Cell and Developmental Biology·Anastasiia A ZakharovaOlga S Ostroumova
Jun 8, 2012·Applied Biochemistry and Biotechnology·Vinod Kumar YataSiddhartha Sankar Ghosh
May 1, 2008·The AAPS Journal·Jarkko RautioJouko Savolainen

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis