[2-C-14] 5-FLUOROURACIL METABOLISM TO [(CO2)-C-14]

The rate of (CO2)-C-14 production from 2-C-14-5-FU was measured in rats bearing the Novikoff ascites hepatoma. Tracer amounts were injected and (CO2)-C-14 collected over a 6-hour period. As the tumor cells proliferated the rate of 2-C-14-5-FU oxidation decreased markedly over the approximately 12 +/- 2 days between implantation of tumor cells and death. On the day of innoculation of tumor cells, oxidation proceeded nearly linearly until almost 50% of the injected 2-C-14-5-FU was converted to (CO2)-C-14 in about 4 hours. With time after tumor innoculation, the rate of (CO2)-C-14 collection declined; ten days after innoculation only about 27% was oxidized by 4 hours, and at the terminal stage it declined to about 18% over 4 hours. Calculated from the time curves, the time oxidation of 25% of the injected trace dose increased from 88 +/- 27 min to 195 +/- 42 min after ten days, to 300 +/- 59 min at the moribund state after 12 +/- 2 days. Similar decreases in oxidation rate of 5-FU were observed during growth of a solid implanted mammary carcinoma and for two other 2-C-14-labelled pyrimidines, uracil and thymine injected in trace quantities. By comparing cancer subjects with themselves at different time-intervals from the onset of the disease and treatment, it might be possible to guage treatment dosages in the progress of the disease.