Pathological features and pyrimidine nucleotide synthesis in human gastric carcinomas

5-Fluorouracil, a potent anticancer drug, is clinically known to be more effective on a poorly differentiated gastric carcinoma than on a well-differentiated type. We investigated activities of thymidylate synthetase (TS) and thymidine kinase (TK) involved in de novo and salvage pathways, respectively, for pyrimidine nucleotide synthesis and histological features in 57 human gastric carcinomas. The average activities of TS in 28 poorly differentiated carcinomas and TK in 29 well-differentiated type were significantly increased to 128 and 166%, respectively, of those in normal gastric mucosa. The TK/TS ratio in the well-differentiated type was 1.7-fold higher than that in the poorly-differentiated type. Therefore, the de novo pathway for pyrimidine nucleotide synthesis is so predominant in a poorly differentiated carcinoma, but not in a well-differentiated type, that the potent TS inhibitor 5-FU or its derivatives are suggested to suppress the growth of the poorly-differentiated gastric carcinoma.