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  • Title: Effects of 5-FU on DNA synthesis and cytotoxicity of human lymphocytes induced by IL-2, TGF-beta3 and PGE2.
    Author: Eisenthal A, Eytan K, Brazowski E, Gitstein G, Greenberg R, Skornick Y.
    Journal: Anticancer Res; 2009 Oct; 29(10):3925-30. PubMed ID: 19846930.
    Abstract:
    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 microM 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 E(2) (PGE(2)) and transforming growth factor (TGF)-beta3. RESULTS: The co-stimulatory effect of 2.5 microM 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-beta3 and PGE(2) 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-beta3 and 10 microM PGE(2). CONCLUSION: Low 5-FU concentrations increase DNA synthesis in lymphocytes and exert a co-stimulatory activity on TGF-beta3 and PGE(2) modulation of IL-2-activated lymphocytes.
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