VARIATIONS IN RADIATION SENSITIVITY AND REPAIR AMONG DIFFERENT HEMATOPOIETIC STEM-CELL SUBSETS FOLLOWING FRACTIONATED-IRRADIATION

JD DOWN*, A BOUDEWIJN, R VANOS, HD THAMES, RE PLOEMACHER

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

66 Citations (Scopus)
128 Downloads (Pure)

Abstract

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 (LD(50/30)) 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. (C) 1995 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)122-127
Number of pages6
JournalBlood
Volume86
Issue number1
Publication statusPublished - 1-Jul-1995

Keywords

  • COLONY-FORMING CELLS
  • BONE-MARROW
  • DOSE-RATE
  • REPOPULATING ABILITY
  • NORMAL-TISSUES
  • CFU-S
  • MOUSE
  • ENGRAFTMENT
  • SEPARATION
  • INVITRO

Cite this