Selective augmentation of radiation effects by 5-fluorocytosine on murine B16(F10) melanoma cells transfected with cytosine deaminase gene.
We report that in vitro 5-fluorocytosine sensitizes B16(F10) melanoma cells to radiation damage when they are transfected with cytosine deaminase gene (CD). The greatest enhancement of radiation cytotoxicity was observed when B16(F10)/CD cells were incubated in medium with 500 microM 5-fluorocytosine for 3 hours, with incubation starting 1 hour after irradiation. 5-Fluorocytosine did not change radiosensitivity of parental, nontransfected cells. The isoeffective dose for CD-transfected cells treated with 5-fluorocytosine was reduced by 20% at a 2-Gy level of effect for nontransfected cells. We believe that the observed outcome is related to 5-fluorouracil generated by CD and subsequent 5-fluorouracil anabolites. Our results support the development of in vivo models for tumor radiosensitization using the CD gene/5-fluorocytosine system.
Szary
J
J
Department of Tumor Biology, Institute of Oncology, Gliwice, Poland.
Missol
E
E
Tarnawski
R
R
Szala
S
S
D000818:Animals; D043525:Cytosine Deaminase; D005437:Flucytosine / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D008546:Melanoma, Experimental / Q000235:genetics* / Q000532:radiotherapy*; D051379:Mice; D009700:Nucleoside Deaminases / Q000235:genetics*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase