Host Interactions in the Effects of 5-Fluorouracil on Ehrlich Ascites Tumor Cells1

5-Fluorouracil (5-FUra) inoculated i.p. into Ehrlich ascites tumor (EATU)-bearing mice inhibited in vivo tumor cell prolif eration and generated a population of EATU cells with half their normal content of DNA. The appearance of aberrant (approxi mately 2C) EATU cells from a normally aneuploid (approxi mately 4C) tumor cell line appeared to require a radiosensitive host cell population, since prior irradiation of animals later given injections of 5-FUra and EATU cells resulted in signifi cantly fewer 2C tumor cells when compared with unirradiated tumor bearers. In contrast, when EATU cells were pulsed with 5-FUra and cultured in vitro, no 2C peak could be detected. Furthermore, results from adoptive transfer experiments showed that EATU cells incubated in vitro with 5-FUra gave rise to far fewer aberrant 2C EATU cells when injected into irradiated, as compared to normal, animals. Cell cycle analyses of peritoneal exÃodate cells from irradiated and normal 5-FUratreated EATU bearers showed that, in addition to possessing few or no 2C tumor cells of reduced DNA content, irradiated animals possessed, within the remaining aneuploid EATU pop ulation, a high percentage of cells in the G2-M phase. There fore, in 5-FUra-treated EATU bearers, a host cell population appeared to be necessary for the tumoricidal induction of 2C tumor cells as well as the inhibition of proliferating G2-M cells within the remaining population of aneuploid tumor cells. Fur ther experiments are being conducted to confirm preliminary observations of macrophage-mediated host cell participation in the generation of tumor cells of reduced ploidy and in the alteration in the cell cycle distribution of the surviving tumor cells. Generation of tumor cells of reduced ploidy may be the cause or the result of a host-mediated tumoricidal mechanism.