Studies on fluorinated pyrimidines. II. Effects on transplanted tumors.

Abstract

1. The activity of a new series of fluorinated pyrimidines has been screened against several transplanted tumors. 2. In general, the activity of 5-fluorouracil was greater than that of 5-fluoroorotic acid. 5-Fluorocytosine, 2-methylmercapto-5-fluorouracil, and 2-thio-5-fluorouracil did not have appreciable tumor-inhibitory activity. 3. The toxicity of 5-fluorouracil was characterized by delayed deaths, hematopoietic depression, diarrhea, weight loss, and hemorrhages in the lungs and intestines. 4. These compounds acted as tumor growthinhibitors rather than as carcinolytic substances. 5. The activity of 5-fluorouracil was considerably greater than that of 6-mercaptopurine and OPSPA on the Ehrlich ascites carcinoma, Novikoff hepatoma, and L1210 leukemia, and less than either or both of those compounds on Sarcoma 180, 755 and E 0771 mammary adenocarcinomas, Sarcoma A-1, Flexner-Jobling carcinoma, Walker 256 carcinosarcoma, and Yoshida ascites sarcoma. 6. Some potentiation of activity against the solid tumors has been obtained when 5-fluorouracil was combined with 6-mercaptopurine, 5-bromouracil, or x-ray treatment.