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Engraftment of bone marrow cells into normal unprepared hosts: effects of
5-fluorouracil and cell cycle status
HS Ramshaw, SS Rao, RB Crittenden, SO Peters, HU Weier and PJ Quesenberry
Cancer Center, University of Massachusetts Medical Center, Worcester, USA.
Bone marrow from animals treated with 5-fluorouracil (5FU) competes equally
with normal marrow when assessed in vivo in an irradiated mouse, but shows
markedly defective engraftment when transplanted into noncytoablated hosts.
Using Southern Blot analysis and a Y-chromosome specific probe, we
determined the level of engraftment of male donor cells in the bone marrow,
spleen, and thymus of unprepared female hosts. We have confirmed the
defective engraftment of marrow harvested 6 days after 5FU (FU-6) and
transplanted into unprepared hosts and shown that this defect is transient;
by 35 days after 5FU (FU-35), engraftment has returned to levels seen with
normal marrow. FU-6 marrow represents an actively cycling population of
stem cells, and we hypothesize that the cycle status of the stem cell may
relate to its capacity to engraft in the nonirradiated host. Accordingly,
we have evaluated the cycle status of engrafting normal and FU-6 marrow
into normal hosts using an in vivo hydroxyurea technique. We have shown
that those cells engrafting from normal marrow and over 70% of the cells
engrafting from FU-6 marrow were quiescent, demonstrating no killing with
hydroxyurea. We have also used fluorescent in situ hybridization (FISH)
analysis with a Y-chromosome probe and demonstrated that normal and
post-5FU engraftment patterns in peripheral blood were similar to those
seen in bone marrow, spleen, and thymus. Altogether these data indicate
that cells engrafting in normal, unprepared hosts are dormant, and the
defect that occurs after 5FU is concomitant with the induction of these
cells to transit the cell cycle.
Volume 86,
Issue 3,
pp. 924-929,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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