Variations in radiation sensitivity and repair among different hematopoietic stem cell subsets following fractionated irradiation.
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.
Down
J D
JD
Department of Radiobiology, University of Groningen, The Netherlands.
Boudewijn
A
A
van Os
R
R
Thames
H D
HD
Ploemacher
R E
RE
D001853:Bone Marrow / Q000528:radiation effects*; D001854:Bone Marrow Cells; D003037:Cobalt Radioisotopes; D003114:Colony-Forming Units Assay; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006412:Hematopoietic Stem Cells / Q000528:radiation effects*; D007928:Lethal Dose 50; D011829:Radiation Dosage; D011836:Radiation Tolerance; D014916:Whole-Body Irradiation
D003037:Cobalt Radioisotopes