Effects of 5-fluorouracil on human mitogen-activated peripheral blood lymphocytes from healthy individuals.
BACKGROUND
The effect of 5-fluorouracil (5-FU) on activated lymphocytes was explored.


METHODS
The in vitro effects of 5-FU on DNA synthesis in mitogen-activated lymphocytes from healthy volunteers were compared to those of the antimetabolites doxorubicin, cyclophosphamide and 6-mercaptopurine. These effects were assessed by alterations in the phenotypic profile and the percentage of cells in various phases of the cell cycle, as well as by the secretion of T helper (Th)1 and Th2 cytokines (ELISA).


RESULTS
Unlike 5-FU, the other antimetabolites failed to augment DNA synthesis in activated lymphocytes. The effect of 5-FU correlated with an increase in the percentage of cells in the S-phase and caused an increased in CD4+ cells, a decrease in CD56+ cells and a shift of the cytokine secretion pattern from Th2 to Th1.


CONCLUSIONS
5-FU exhibited a unique effect on DNA synthesis in activated lymphocytes which was accompanied by selective effects on various lymphocyte subpopulations.
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
Katz
Ben-Zion
BZ
Shirazi
Idit
I
Skornick
Yehuda
Y
D002453:Cell Cycle / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D004247:DNA / Q000096:biosynthesis / Q000097:blood; D004317:Doxorubicin / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma; D016753:Interleukin-10; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D015122:Mercaptopurine / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011043:Pokeweed Mitogens / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D007376:Interleukin-2; D008934:Mitogens; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D016753:Interleukin-10; D004317:Doxorubicin; D007371:Interferon-gamma; D003520:Cyclophosphamide; D004247:DNA; D015122:Mercaptopurine; D005472:Fluorouracil