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.