Effects of 5-FU on DNA synthesis and cytotoxicity of human lymphocytes induced by IL-2, TGF-beta3 and PGE2.
BACKGROUND
Low 5-fluorouracil (5-FU) concentrations cause a significant increase in DNA synthesis in mitogen-activated human lymphocytes.


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).


CONCLUSIONS
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.
Eisenthal
Avi
A
Department of Pathology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. eisenthal@tasmc.health.gov.il
Eytan
Karin
K
Brazowski
Eli
E
Gitstein
Gilad
G
Greenberg
Ron
R
Skornick
Yehuda
Y
D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis* / Q000097:blood; D015232:Dinoprostone / Q000494:pharmacology*; D004347:Drug Interactions; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D013936:Thymidine / Q000096:biosynthesis / Q000097:blood; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*
D003470:Culture Media; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D053782:Transforming Growth Factor beta3; D004247:DNA; D015232:Dinoprostone; D005472:Fluorouracil; D013936:Thymidine