RT Journal Article
SR Electronic
T1 Effects of 5-FU on DNA Synthesis and Cytotoxicity of Human Lymphocytes Induced by IL-2, TGF-β3 and PGE<sub>2</sub>
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3925
OP 3930
VO 29
IS 10
A1 AVI EISENTHAL
A1 KARIN EYTAN
A1 ELI BRAZOWSKI
A1 GILAD GITSTEIN
A1 RON GREENBERG
A1 YEHUDA SKORNICK
YR 2009
UL http://ar.iiarjournals.org/content/29/10/3925.abstract
AB Background: Low 5-fluorouracil (5-FU) concentrations cause a significant increase in DNA synthesis in mitogen-activated human lymphocytes. Materials and Methods: We explored 2.5 μM 5-FU-induced DNA synthesis by testing 5-FU activity in hypoxanthine-aminopterin-thymidine (HAT)-containing medium, and its effect on thymidylate synthase (TS) activity and CD25 expression in interleukin (IL)-2-activated human peripheral blood mononuclear cells (PBMCs) and the combined effects with prostaglandin E2 (PGE2) and transforming growth factor (TGF)-β3. Results: The co-stimulatory effect of 2.5 μM 5-FU on DNA synthesis was abrogated in HAT-cultured medium. 5-FU substantially reduced TS activity by 50% in IL-2-activated PBMCs. 5-FU combined with TGF-β3 and PGE2 did not alter their inhibitory effects on IL-2-activated natural killer cell cytotoxicity, but substantially affected increased DNA synthesis of cells cultured in IL-2 and co-cultured with 10 ng/ml TGF-β3 and 10 μM PGE2. Conclusion: Low 5-FU concentrations increase DNA synthesis in lymphocytes and exert a co-stimulatory activity on TGF-β3 and PGE2 modulation of IL-2-activated lymphocytes.