In the mouse hematopoietic system, 5-fluorouracil (5-FU) reversibly in
hibits the generation of multilineage colonies containing granulocyte,
erythroid, megakaryocyte, and macrophage lineage. To determine the ef
fect of 5-FU on mastopoiesis in vitro, bone marrow cells were obtained
from mice, cultured, and treated with 5-FU for 14 days in an interleu
kin-3 (IL-3)-enriched medium. A dose-related inhibitory effect of 5-FU
on mastopoiesis was found. When an inhibitory dose (1 mu/mL) of 5-FU
was supplemented to the cultures for only 2, 4, or 8 days and the cell
s were then recultured without the drug, we observed inhibition of mas
topoiesis directly related to the time of exposure of the cells to 5-F
U.To determine the effect of 5-FU on mastopoiesis in vivo, bone marrow
cells from mice that had received a single intravenous (IV) 5-FU inje
ction (150 mg/kg) were cultured. A virtually total absence of mast cel
ls was noted at days 1 and 2 following 5-FU administration. A gradual
reappearance of mast cells was later observed. Whether mice were injec
ted with the drug once or with four once-daily (100 mg/kg 5-FU) inject
ions, a similar pattern of delay of mast cell appearance was observed.
The findings suggest (1) an irreversible, nonadditive, toxic effect o
f 5-FU on mast cell precursors and (2) that most or all of the mast ce
ll precursors are nonquiescent cells, continuously activated or cyclin
g. In addition, the use of 5-FU may serve as a unique model system for
controlling and studying mastopoiesis in normal mice, rather than the
mutated mice currently studied.