Thymidylate synthase from untreated human colorectal cancer and colonic mucosa: Enzyme activity and inhibition by 5-fluoro-2′-deoxyuridine-5′-monophosphate

Godefridus J. Peters, Cees J. van Groeningen, Emile J. Laurensse, Herbert M. Pinedo

Research output: Contribution to journalArticle

Abstract

Inhibition of thymidylate synthase (TS) by the 5-fluorouracil (5-FU) metabolite FdUMP is considered to be the main mechanism of action of 5-FU. TS from colorectal tumours and normal colon mucosa from 10 untreated patients was studied. There was a large variation in the activity of tumour TS both at 1 and 10 μmol/1 of its substrate dUMP; in normal mucosa this variation was less. Inhibition by 10 nmol/l FdUMP in tumours varied from 80 to 90% at 1 μmol/l dUMP; in normal mucosa, inhibition varied from 10 to 80%. The number of FdUMP binding sites ranged from 0.1 to 1 in tumours but such binding sites were not detectable in normal mucosa. The ratio between TS activity and FdUMP binding sites varied considerably in tumours but not in normal mucosa. The deviations from normal kinetics may represent a mutant TS form. Alterations in TS may partly account for differences in response to 5-FU.

Original languageEnglish (US)
Pages (from-to)263-267
Number of pages5
JournalEuropean Journal of Cancer and Clinical Oncology
Volume27
Issue number3
DOIs
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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