[Effects of hyperthermochemotherapy on activities of DNA-synthesizing enzymes in 1, 2-dimethylhydrazine (DMH)-induced colon carcinomas in rats].

Abstract

It has been known that a high incidence of adenocarcinoma in distal colon can be induced by s.c. injection of 1, 2-dimethylhydrazine (DMH) into rats at weekly intervals. We investigated effects of radiofrequency hyperthermia (RF-HT) in combination with anti-cancer drug UFT (a combination of tegafur and uracil) on activities of DNA-synthesizing enzymes, using colon carcinomas induced by DMH treatment in rats. 1) Thymidylate synthetase (TS), DNA-synthesizing enzyme in de novo pathway of pyrimidine metabolism, increased to approximately 7-fold that of normal control colon in DMH-induced colon carcinomas in activity, but was markedly reduced to 48% of that in the carcinomas by administration of UFT. 2) Thymidine kinase (TK) in salvage pathway increased to approximately 8-fold that of the control in the carcinomas in activity, but was markedly reduced to 25% of that in the carcinomas by RF-HT treatment. 3) The TK-isozyme, that was thought to be a fetal type in the intracellularly cytoplasmic fraction and closely involved in rapid DNA replication, increased to approximately 24-fold that of the control in the carcinomas in activity, but was reduced to the nearly same level as that of the control by RF-HT treatment. This isozyme was labile in thermostability and easy to be inactivated in low pH. 4) The activities of TS and TK in the carcinomas were extremely suppressed by UFT administration in combination with RF-HT treatment. These results indicate that hyperthermochemotherapy with UFT may serve as an available treatment for colon carcinomas.