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 deam inase gene (CD). The greatest enhancement of radiation cytotoxicity wa s observed when B16(F10)/CD cells were incubated in medium with 500 mu M 5-fluorocytosine for 3 hours, with incubation starting 1 hour after irradiation. 5-Fluorocytosine did not change radiosensitivity of pare ntal, nontransfected cells, The isoeffective dose for CD-transfected c ells treated with 5-fluorocytosine was reduced bp 20% at a 2-Gy level of effect for nontransfected cells. We believe that the observed outco me is related to 5-fluorouracil generated by CD and subsequent 5-fluor ouracil anabolites. Our results support the development of in vivo mod els for tumor radiosensitization using the CD gene/5-fluorocytosine sy stem.