Role of platelet derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity and potential role of deoxyribose-1-phosphate

M de Bruin, T van Capel, K Smid, K van der Born, M Fukushima, K Hoekman, H M Pinedo, G J Peters

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Thymidine phosphorylase (TP) catalyzes the phosphorolytic cleavage of thymidine (TdR) to thymine and deoxyribose-1-phosphate (dR-1-P). TP, which is overexpressed in a wide variety of solid tumors, is involved in the activation and inactivation of fluoropyrimidines. We investigated the role of TP in 5'-deoxy-5-fluorouridine (5'DFUR), 5-fluorouracil (5FU) and trifluorothymidine (TFT) sensitivity. TP had no effect on TFT while it activated 5'DFUR and to a lesser extent 5FU. In order to provide an explanation for this difference in activation of 5'DFUR and 5FU, we studied the role of the 5FU co-substrate, dR-1-P, needed for its activation.

Original languageEnglish
Pages (from-to)1485-90
Number of pages6
JournalNucleosides and Nucleotides
Volume23
Issue number8-9
DOIs
Publication statusPublished - Oct 2004
Externally publishedYes

Keywords

  • Antimetabolites, Antineoplastic/pharmacology
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Fluorouracil/pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Neoplasms/drug therapy
  • Pyrimidines/pharmacology
  • Ribosemonophosphates/physiology
  • Thymidine Phosphorylase/physiology
  • Time Factors
  • Transfection

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