IN-SITU RADIATION SENSITIVITY OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR-RECRUITED MURINE CIRCULATING BLOOD AND BONE-MARROWPROGENITORS (COLONY-FORMING UNIT [CFU]-GRANULOCYTE-MACROPHAGE AND CFU-MEGAKARYOCYTE) - EVIDENCE FOR POSSIBLE BIOLOGIC DIFFERENCES BETWEEN MOBILIZED BLOOD AND BONE-MARROW

Increasing evidence especially stemming from peripheral blood progenit or transplantation studies points to a possible biologic difference be tween mobilized blood and bone marrow progenitor cells. The objective of this study was to compare the in situ radiation sensitivity of reco mbinant human granulocyte colony-stimulating factor (rhG-CSF)-recruite d circulating granulopoietic (blood colony-forming unit-granulocyte-ma crophage [CFU-GM(blood)]) and megakaryocytopoietic (blood CFU-megakary ocyte [CFU-Meg(blood)]) progenitors, with the nonmobilized fraction re maining in the bone marrow (CFU-GM(femur) and CFU-Meg(femur)). Splenec tomized male B6D2F1 mice received 50 mu g/kg/d rhG-CSF daily for 8 day s to induce high levels of circulating progenitors, followed by either total body X-irradiation (TBI) or X-irradiation of the chest (CI) wit h 62.5, 125, 250, or 500 cGy. Progenitor cells were assayed 24 hours a fter irradiation. circulating CFU-GM and CFU-Meg in the blood were dec reased in a dose-dependent fashion by both TBI and CI, with TBI causin g greater damage than CI. Average D-0 values for TBI were 53 cGy for C FU-GM(blood) and 40 cGy for CFU-Meg(blood) D-0 values for Ci were 90 c Gy 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) (D-0, 136 cGy) and CFU-Meg(femur) (D-0 148 cGy). However, radi ation-induced bone marrow progenitor cell kill was significantly lower when compared with blood progenitors. Despite the fact that circulati ng blood elements only received a fraction of the total dose administe red as CI, the extent of blood progenitor kill caused by CI was higher than the effects of identical TBI doses on bone marrow CFU. The resul ts of this study showed that rhG-CSF-recruited CFU-Meg(blood) and CFU- GM(blood) were considerably more radiosensitive than femoral progenito rs, thereby providing novel evidence for a biologic difference between rhG-CSF-recruited peripheral blood progenitors and the nonrecruited b one marrow CFU. (C) 1996 by The American Society of Hematology.