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S Scheding, JE Media, MA KuKuruga and A Nakeff
Division of Hematology and Oncology, Wayne State University, School of
Medicine, Detroit, MI 48201, USA.
Increasing evidence especially stemming from peripheral blood progenitor
transplantation studies points to a possible biologic difference between
mobilized blood and bone marrow progenitor cells. The objective of this
study was to compare the in situ radiation sensitivity of recombinant human
granulocyte colony-stimulating factor (rhG-CSF)-recruited circulating
granulopoietic (blood colony-forming unit-granulocyte-macrophage
[CFU-GM(blood)]) and megakaryocytopoietic (blood CFU-megakaryocyte
[CFU-Meg(blood)]) progenitors, with the nonmobilized fraction remaining in
the bone marrow (CFU-GM(femur) and CFU-Meg(femur)). Splenectomized male
B6D2F1 mice received 50 micrograms/kg/d rhG-CSF daily for 8 days to induce
high levels of circulating progenitors, followed by either total body
X-irradiation (TBI) or X-irradiation of the chest (CI) with 62.5, 125, 250,
or 500 cGy. Progenitor cells were assayed 24 hours after irradiation.
Circulating CFU-GM and CFU-Meg in the blood were decreased in a dose-
dependent fashion by both TBI and CI, with TBI causing greater damage than
CI. Average D0 values for TBI were 53 cGy for CFU-GM(blood) and 40 cGy for
CFU-Meg(blood) D0 values for CI were 90 cGy for CFU-GM(blood) and 140 cGy
for CFU-Meg(blood). As seen for blood progenitor cells, TBI caused a
dose-dependent decrease of both CFU-GM(femur) (D0, 136 cGy) and
CFU-Meg(femur) (D0, 148 cGy). However, radiation-induced bone marrow
progenitor cell kill was significantly lower when compared with blood
progenitors. Despite the fact that circulating blood elements only received
a fraction of the total dose administered as Cl, the extent of blood
progenitor kill caused by Cl was higher than the effects of identical TBI
doses on bone marrow CFU. The results of this study showed that
rhG-CSF-recruited CFU-Meg(blood) and CFU-GM(blood) were considerably more
radiosensitive than femoral progenitors, thereby providing novel evidence
for a biologic difference between rhG-CSF- recruited peripheral blood
progenitors and the nonrecruited bone marrow CFU.
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| Copyright © 1996 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||