Thymidylate synthetase and thymidine kinase activities in DMH-induced colon carcinomas in rats and effects of UFT.

S. Sakamoto, N. Kasahara, T. Kawasaki, H. Kudo, R. Okamoto, Y. Kawachi, S. Murakami, T. Iwama, K. Yaegashi, Y. Mishima

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Abstract

Carcinoma of the colon was induced in rats by injection of a carcinogen 1,2-dimethylhydrazine (DMH), and thymidylate synthetase (TS) and thymidine kinase (TK) activities, which catalyze the biosynthesis of dTMP by the de novo pathway and the salvage pathway of pyrimidine synthesis, respectively, were measured in normal control colon, DMH-treated normal colon, and DMH-induced colon carcinoma with or without administration of two doses of an anti-cancer drug UFT (a combination of tegafur and uracil). TS and TK activities were both increased after treatment with DMH, markedly in colon carcinoma tissue, and to a lesser degree in normal-appearing colon tissue. This phenomenon is well explained by the hypothesis that biochemical alterations of DNA-synthesizing enzyme activities occur as a preliminary step prior to the development of overt cancerous transformation. A low dose of UFT inhibited TS activity but enhanced TK activity, therefore, the salvage pathway may compensate for the reduced level of the de novo synthesis. On the other hand, a large dose of UFT reduced both TS and TK activities, perhaps due to cytotoxic effects of UFT incorporation into RNA.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalThe Bulletin of Tokyo Medical and Dental University
Volume33
Issue number4
StatePublished - Dec 1 1986
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

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Sakamoto, S., Kasahara, N., Kawasaki, T., Kudo, H., Okamoto, R., Kawachi, Y., Murakami, S., Iwama, T., Yaegashi, K., & Mishima, Y. (1986). Thymidylate synthetase and thymidine kinase activities in DMH-induced colon carcinomas in rats and effects of UFT. The Bulletin of Tokyo Medical and Dental University, 33(4), 137-144.