Thymidylate synthetase activity and fluorouracil sensitivity of human colonic cancer and normal mucosal tissue preparations
- 15 March 1981
- Vol. 47 (6) , 1313-1317
- https://doi.org/10.1002/1097-0142(19810315)47:6<1313::aid-cncr2820470613>3.0.co;2-o
Abstract
This study compares thymidylate synthetase activity and certain aspects of fluorinated pyrimidine metabolism in tissue preparations derived from human colonic adenocarcinoma and from normal colonic mucosa. The purpose was to define differences that might be sufficient to explain the selective antitumor response of some colonic adenocarcinomas to 5‐fluorouracil (FU) chemotherapy. Some carcinomas had much greater thymidylate synthetase activity than did other carcinomas and all normal mucosal preparations. Such carcinomas may be highly reliant on thymidylate synthetase and hence susceptible to its inhibition. Similarly, the smaller amount of FdUMP dephosphorylation found in all carcinomas compared with autologous normal mucosal preparations might result in prolonged thymidylate synthetase inhibition. In addition, greater thymidylate synthetase inhibition was produced by 1 × 10−4M FU in an occasional tumor than was found in normal mucosal preparations.This publication has 14 references indexed in Scilit:
- Single-step phosphorylation of 5-fluoro-2'-deoxyuridine to 5-fluoro-2'-deoxyuridine 5'-phosphateJournal of Medicinal Chemistry, 1974
- Synthesis of 5-fluorouridine 5′-phosphate by a pyrimidine phosphoribosyltransferase of mammalian origin—II. Correlation between the tumor levels of the enzyme and the 5-fluorouracil-promoted increase in survival of tumor-bearing miceBiochemical Pharmacology, 1969
- Nucleotide Formation as a Determinant of 5-Fluorouracil Response in Mouse LeukemiasScience, 1966
- An Isotopic Assay for Thymidylate Synthetase*Biochemistry, 1966
- Studies on resistance against 5-fluorouracil IV. Evidence for an altered uridine kinase in resistant cellsBiochimica et Biophysica Acta (BBA) - Specialized Section on Nucleic Acids and Related Subjects, 1963
- Studies concerning the inhibition of cellular reproduction by deoxyribonucleosides: I. Inhibition of the synthesis of deoxycytidine by a phosphorylated derivative of thymidineBiochimica et Biophysica Acta (BBA) - Specialized Section on Nucleic Acids and Related Subjects, 1963
- Studies on Fluorinated PyrimidinesJournal of Biological Chemistry, 1961
- Studies concerning inhibition of the synthesis of deoxycytidine by phosphorylated derivatives of thymidineBiochimica et Biophysica Acta, 1960
- Possible Enzymic Mechanism for the Development of Resistance against Fluorouracil in Ascites TumoursNature, 1959
- The Determination of Enzyme Dissociation ConstantsJournal of the American Chemical Society, 1934