Studies on the metabolism of thymine-2-C14 by the rat.

It has been clearly established (1, 2), through the use of N16-labeled material, that the utilization of free thymine for the synthesis of deoxyribonucleic acid (DNA) by the rat is extremely limited. However, these studies afforded but little information concerning the rate and extent of the metabolism of thymine. In the experiments reported here, thymine-204 has been found to be more rapidly and extensively catabolized by this species than was heretofore appreciated. In marked contrast to the results obtained after administration of uracil-N15 and thymine-N15 to rats (2), and of uracil-N15 to human subjects (3), only a small amount, of the tracer was found to be excreted via the urine. A large portion (55 per cent) of the isotope was excreted, however, in the respiratory COz during a period of 4 hours following intraperitoneal administration of thymine-2-Cl4. Experiments with rat liver slices also have shown that thymine-2-C*4 is rapidly catabolized by this tissue to give rise to C402. In agreement with the findings of Brown, Roll, and Weinfeld (I), a small but significant amount of the administered isotope was found in the thymine moiety of DNA of regenerating rat liver, and a lesser amount in the DNA of other tissues.