Relative activities of thymidylate synthetase and thymidine kinase in 1,2-dimethylhydrazine-induced colon carcinomas in rats.

Abstract

Thymidylate synthetase (TS) and thymidine kinase (TK) are known to catalyse the methylation of dUMP for the de novo synthesis of dTMP and the phosphorylation of thymidine for the salvage synthesis of dTMP in the pyrimidine pathway, respectively. High TS and TK activities and the existence of TK isozymes have been observed in rapidly proliferating tissues. TS and TK activities in 1,2-dimethylhydrazine (DMH)-induced colon carcinomas in rats increased significantly to 331 and 207% of the activities in normal colon, respectively, and were well correlated inversely (y = -0.93x + 5.24), with a correlation coefficient of -0.787. The colonic TK isozymes were separated into two types by DEAE-cellulose column chromatography. The TK isozyme eluted from the column by the elution buffer alone without NaCl was markedly higher (23.6-fold) in activity in DMH-induced colon carcinoma than in normal control colon and was not affected by deoxycytidine triphosphate. This isozyme, whose mol. wt is 100,000 by h.p.l.c., is thought to be closely involved in rapid DNA replication. These results indicate that early biochemical changes in DMH-induced colon carcinoma in rats may serve as a useful model and provide valuable insight into the mechanisms involved in colonic carcinogenesis.