Sensitivity of human KB cells expressing platelet-derived endothelial cell growth factor to pyrimidine antimetabolites.
Thymidine phosphorylase (dThdPase) is an enzyme involved in pyrimidine nucleoside metabolism. However, little is known about its physiological functions. We previously purified dThdPase from human placenta, isolated a complementary DNA clone for this enzyme, and sequenced it. There was complete sequence identity between 120 amino acids of human dThdPase and the sequence of platelet-derived endothelial cell growth factor (PD-ECGF). Human KB epidermal carcinoma cells transfected with platelet-derived endothelial cell growth factor complementary DNA expressed a 55-kDa protein that was detected with anti-dThdPase antibody and the cell lysate had dThdPase activity. The sensitivity of transfected cells to the antimetabolites was compared with that of untransfected KB cells. The sensitivity of the transfected cells to Doxifluridine (5'-deoxy-5-fluorouridine) was higher than that of untransfected KB cells. Transfected cells were also more sensitive to Tegafur than untransfected KB cells. These results demonstrate that dThdPase is involved in the activation of these anticancer agents. Since many cancer tissues contain high dThdPase activity compared with normal tissues, these transfected and untransfected KB cells are useful for studying the role of dThdPase in the activation of pyrimidine antimetabolites and also in angiogenesis.
Haraguchi
M
M
Institute for Cancer Research, Faculty of Medicine, Kagoshima University, Japan.
Furukawa
T
T
Sumizawa
T
T
Akiyama
S
S
D002455:Cell Division; D005467:Floxuridine / Q000494:pharmacology; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D005641:Tegafur / Q000494:pharmacology; D013937:Thymidine Kinase / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000502:physiology*; D014162:Transfection
D005467:Floxuridine; D005641:Tegafur; D012313:RNA; D013939:Thymidine Phosphorylase; D013937:Thymidine Kinase; D005472:Fluorouracil; C025034:doxifluridine