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Variations in radiation sensitivity and repair among different
hematopoietic stem cell subsets following fractionated irradiation
JD Down, A Boudewijn, R van Os, HD Thames and RE Ploemacher
Department of Radiobiology, University of Groningen, The Netherlands.
The radiation dose-survival of various hematopoietic cell subsets in murine
bone marrow (BM) was determined in the cobblestone area forming cell (CAFC)
assay under conditions of single-, split-, and multiple- dose irradiation.
A greater recovery in cell survival with decreasing dose per fraction, or
increasing fraction number, was observed for primitive CAFC day-28 and
day-35 than for CAFC day-6 and day-12 (colony- forming unit
(CFU)-granulocyte macrophage and CFU-spleen day-12 equivalents). Linear
quadratic (LQ) model analysis of CAFC survival data provided an estimate of
the alpha/beta ratio that is an inverse index of the fractionation effect
and is known to be lower for late than for acutely responding tissues. This
analysis gave decreasing alpha/beta ratios with increasing primitiveness of
the CAFC subset. These values were found to be comparatively low (about 4
Gy) for CAFC day-28 and day-35 and are in general agreement with previous
studies on long-term repopulation in vivo. In contrast, alpha/beta ratios
of CAFC day-6 and day-12 were relatively high (above 6 Gy) and are
consistent with values obtained from acute marrow failure. Delayed
harvesting of BM after a single dose of 6 Gy showed little evidence of
proliferative repopulation over 1 week and hence the differential
dose-sparing effect of fractionation among the CAFC subsets appears to be
mostly attributable to the influence of sublethal damage repair. These
results require a reevaluation of previous notions of marrow stem cell
radiosensitivity and repair based on acute marrow lethality (LD50/30) or
spleen colony (CFU-S) data, especially when applied to fractionated total
body irradiation effects on long-term repopulating stem cells in a BM
transplant setting.
Volume 86,
Issue 1,
pp. 122-127,
07/01/1995
Copyright © 1995 by The American Society of Hematology
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