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Most primitive hematopoietic stem cells are stimulated to cycle rapidly
after treatment with 5-fluorouracil
DE Harrison and CP Lerner
Jackson Laboratory, Bar Harbor, ME 04609-0800.
To test whether primitive hematopoietic stem cells (PHSC) cycle rapidly
during recovery from an initial 5-fluorouracil (5-FU) treatment, two doses
of 5-FU were administered 1, 3, 5 or 8 days apart. Cells from treated
marrow donors were mixed with untreated competitor marrow that would
produce genetically distinguishable erythrocytes and lymphocytes, using
hemoglobin (Hb) and glucosephosphate isomerase (GPI) transplantation
markers. These cell mixtures were injected into lethally irradiated hosts.
Functional abilities of donor marrow populations were assessed after 3, 6,
and 12 months as percentages of donor type Hb and GPI in the host's
circulating erythrocytes and lymphocytes, respectively. Bone marrow from
mice treated with two doses of 5-FU 3 to 5 days apart was severely
affected, producing circulating erythroid and lymphoid cells an average of
only 25% of normal for doses 3 days apart, and 14% of normal for doses 5
days apart. Two doses of 5- FU administered 1 day or 8 days apart had much
smaller effects, producing circulating cells 75% or 58% of normal. Thus,
most PHSC are stimulated to proliferate rapidly 3 to 5 days after treatment
with 5- FU, but far fewer PHSC proliferate as early as 1 day, or as late as
8 days, after the 5-FU treatment.
Volume 78,
Issue 5,
pp. 1237-1240,
09/01/1991
Copyright © 1991 by The American Society of Hematology
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