Thiouracil-Pyrimidine Relationships in Thyroid and Other Tissues

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Abstract
An examination was made of several systems in which thiouracil and the pyrimidines, uracil, thymine and orotic acid, might compete. The goitrogenic effects of thiouracil were compared with those of other thiopyrimidines and thiopurines. Only thiopyrimidines exhibited goitrogenic properties with thioorotic acid and thiocytosine being weakly goitrogenic and thiothymine inactive. The goitrogenic properties of thiouracil in an iodine-deficient diet were not reduced by simultaneous administration of daily doses of uracil or thymine 300 and 120 times, respectively, that of thiouracil. The pyrimidines and thiouracil were not degraded to 14CO2 by rat thyroid or calf thymus slices. Rat liver slices rapidly oxidized uracil-2-14C, metabolized orotic acid-6-14C only slightly, and did not appear to degrade thiouracil at all. The addition of thiouracil had no discernible effect on the degradation of uracil. Utilization of uracil for RNA formation by thyroid slices was not altered by the presence of thiouracil but was depressed by thiouracil in liver slices and was especially affected in calf thymus slices. However, orotic acid incorporation into RNA was unaffected by thiouracil. Following administration of thiouracil-2-14C, radioactivity could not be demonstrated in any of the nucleotides of rat liver or thyroid RNA. Similar results were obtained after incubation with slices of these tissues. Incubation of calf thymus slices with thiouracil-2-14C resulted in demonstrations of radioactivity in the UMP fraction amounting to 4.3% as much as seen after incubation with uracil-2-14C and 0.64 % as much as with orotic acid-6-14C. Thiouracil-36S incorporation into RNA could not be demonstrated in any of the preparations, including calf thymus. This observation, in conjunction with the demonstration of uracil-14C formation after incubation with thiouracil-2-14C, suggests that the radioactivity in RNA nucleotides after incubation with thiouracil-2-14C was due to incorporation of uracil rather than thiouracil. (Endocrinology76: 728, 1965)