title: [Influence of the selected pyrimidine compounds on the activity of thymidine phosphorylase from normal and tumor endometrial cells].
abstract: OBJECTIVE
  The aim of this study was to evaluate the influence of the selected pyrimidine compounds on the activity of thymidine phosphorylase (TP) of normal and tumor endometrial cells.
  
  
  METHODS
  Influence of 28 chemical compounds on the TP activity in the cytosol of the endometrial cells was studied by the spectrophotometric method. The studied group comprised postmenopausal women with endometrial cancer: adenocarcinoma endometrialis (Adeno Ca E). The second group included women with normal endometrium after surgery due to non-oncologic reasons.
  
  
  RESULTS
  The most potent inhibitor of TP activity from cancer and endometrium was synthesized 5-bromo-6-acetyloaminouracil, which at the 0.2 mM concentration, by 0.2 mM concentration thymidine reduced the cytosol TP activity by about 80%. 5-bromo-6-aminouracil, 5-nitrouracil and 5-bromouracil reduced this TP activity in statistically significant manner. From among synthesized 1-N-allyloxymethylpyrimidine derivatives 1-N-allyloxymethylthymine was the strongest inhibitor of the TP activity in endometrium, and 1-N-allyloxymethyl-4-hydrokxy-5-nitro-6-oxopyrimidine in endometrial cancer respectively. The most potent activators of TP in endometrial cancer was 5-bromodeoxyuridine and 1-N-allyloxymethyl-5-nitrouracil, which increased the TP activity about 100%. 5-fluorodeoxyuridine, 5-jododeoxyuridine and 2'-deoxyuridine activated the TP in statistically significant manner too, but stronger in case of endometrial cancer than in normal endometrium. The synthesized 5-bromo-6-acetyloaminouracil strongly inhibited the TP activity of endometrial cells and might be useful in reducing endometrial cancer angiogenesis. On the other hand 5-bromodeoxyuridine and the synthesized 1-N-allyloxymethyl-5-nitrouracil might increase the effect of antitumor therapy with the cytostatics. These conclusions ought to be confirmed by analyzing more tumor cases.
authors.affiliation: Zakład Biochemii Medycznej, Katedra Biochemii Medycznej w todzi. zaborska@zdn.umed.lodz.pl
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Miszczak-Zaborska
authors.forename: Monika
authors.initials: M
authors.lastname: Smolarek
authors.forename: Marcin
authors.initials: M
authors.lastname: Dramiński
authors.forename: Robert
authors.initials: R
authors.lastname: Kubiak
authors.forename: Barbara
authors.initials: B
authors.lastname: Józwiak
authors.forename: Jacek
authors.initials: J
authors.lastname: Bartkowiak
mesh_terms: D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011044:Poland; D011743:Pyrimidines / Q000008:administration & dosage* / Q000494:pharmacology; D013053:Spectrophotometry / Q000379:methods; D013939:Thymidine Phosphorylase / Q000187:drug effects / Q000378:metabolism*
chemical_list: D011743:Pyrimidines; D013939:Thymidine Phosphorylase