[2‐ 14 C] 5‐fluorouracil metabolism to [ 14 CO 2 ]

The rate of 14 CO 2 production from 2‐ 14 C‐5‐FU was measured in rats bearing the Novikoff ascites hepatoma. Tracer amounts were injected and 14 CO 2 collected over a 6‐hour period. As the tumor cells proliferated the rate of 2‐ 14 C‐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‐ 14 C‐5‐FU was converted to 14 CO 2 in about 4 hours. With time after tumor innoculation, the rate of 14 CO 2 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‐ 14 C‐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.