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In Vivo Inhibition of Pyrimidine Catabolism by 5-Cyanouracil¹

Department of Microbiology, University of Mississippi School of Medicine, Jackson, Mississippi 39216

The peak in vivo rates of catabolism to ¹⁴CO₂ of uracil-2-¹⁴C and of 5-fluorouracil-2-¹⁴C were delayed from 30 to 90 min in rats when excess thymine or excess 5-cyanouracil were injected together with the labeled compound. The delay was greater with 5-cyanouracil, which is a known inhibitor of rat liver pyrimidine reductase. When the peak output of ¹⁴CO₂ was thus delayed, the total recovery of ¹⁴C decreased in respired CO₂ but increased in the urine, largely as unchanged injected compound. This suggests that blocking the catabolism of pyrimidines can prolong significant circulating levels, although excretion via the urine may limit the maximum levels achieved.

¹ This work was supported by American Cancer Society Grants T-357 and PRA-40 (P. A. M.) and NIH Grants 5-K3-AI-7021 (G. A. G.), 1-F1-GM-33650 (M. T. D.), and Training Grant AI-69. A preliminary report of the main findings was presented at the Tenth International Cancer Congress, held in Houston, Texas, May 22 to 29, 1970.

Received 10/16/70. Accepted 2/23/71.