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 language | English |
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Pages (from-to) | 1485-90 |
Number of pages | 6 |
Journal | Nucleosides and Nucleotides |
Volume | 23 |
Issue number | 8-9 |
DOIs | |
Publication status | Published - Oct 2004 |
Externally published | Yes |
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