Role of platelet derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity and potential role of deoxyribose-1-phosphate.
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.
de Bruin
M
M
Department Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
van Capel
T
T
Smid
K
K
van der Born
K
K
Fukushima
M
M
Hoekman
K
K
Pinedo
H M
HM
Peters
G J
GJ
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D011743:Pyrimidines / Q000494:pharmacology; D012267:Ribosemonophosphates / Q000502:physiology*; D013939:Thymidine Phosphorylase / Q000502:physiology*; D013997:Time Factors; D014162:Transfection
D000964:Antimetabolites, Antineoplastic; D011743:Pyrimidines; D012267:Ribosemonophosphates; C031302:2-deoxyribose 1-phosphate; D013939:Thymidine Phosphorylase; D005472:Fluorouracil