On the mechanism of cytotoxicity of fluorinated pyrimidines in four human colon adenocarcinoma xenografts maintained in immune-deprived mice.

Three fluorinated pyrimidines, 5-fluorouracil (FUra), 5-fluorouridine (FUrd), and 5-fluoro-2'-dexoyuridine (FdUrd), have been studied in four human colonic tumor xenograft lines. The preliminary findings may be summarized as follows: 1) after equimolar dosages, the agent reaching the highest concentration in the tumor produced the highest level of fluorodeoxyuridylate (FdUMP); 2) within a tumor line, the order of response to the three agents is related to the order of FdUMP-generation; 3) the tumor-response did not correspond to the level of analogue-incorporation into RNA; 4) the measurement of levels of free FdUMP in tumors is a poor prognostic indicator of drug-response; and 5) the levels of FdUMP in the tumors are maintained for considerable periods and appear to be dependent upon the maintenance of the levels of either FUra or FUrd, irrespective of the parent agent administered.