Recombinant murine GM-CSF increases resistance of some factor dependent hematopoietic progenitor cells to low-dose-rate gamma irradiation

Abstract

The effects of murine recombinant IL-3 (multi-CSF) and murine recombinant GM-CSF (granulocyte-macrophage colony stimulating factor) on the radiation biology of clonal hematopoietic progenitor cell lines were evaluated. Four clonal cell lines with growth response to either IL-3 or GM-CSF (FDCP-1JL26, and bg/bg d64) or exclusively dependent on IL-3 (32D cl 3 and B6SUtA), were pre-incubated in IL-3, or GM-CSF, for 7 days prior to gamma irradiation, then washed and irradiated at 5 cGy/min, or 116 cGy/min, and transferred to semisolid medium supplemented with either IL-3, or GM-CSF, for assay of 7 day ≥50 cell colonies. The cell lines demonstrated similar radiosensitivity and lack of a detectable dose-rate effect when grown in IL-3 (FDCP-1JL26: D 0 154, n 1.05 at 5 cGy/min, and Do 138, n 1.16 at 116 cGy/min; bg/bg d64: D 0 95.7, n 1.16 at 5 cGy/min, and D 0 97.7, n .993 at 116 cGy/min; B6SUtA: D 0 101, n 1.29 at 5 cGy/min, D 0 100, n 1.27 at 116 cGy/min; and cell line 32D cl 3: D 0 123, n 1.65 at 5 cGy/min, and D 0 126, n 1.17 at 116 cGy/min). In contrast, FRCP-1JL26 cells demonstrated a significant relative radioresistance at low-dose-rate when grown in recombinant GM-CSF, (D 0 217, n 1.27 at 5 cGy/min, D 0 138, n 1.34 at 116 cGy/min, p < .005). The increase in radioresistance of FDCP-1 cells at low-dose-rate was induced either by preincubation in GM-CSF with transfer to IL-3, or by preincubation in IL-3 and transfer to recombinant GM-CSF. Growth factor independent malignant subclones of lines B6SUtA and FRCP-1JL26 demonstrated a significant increase in radioresistance at low-dose-rate (B6SUtA EL4JL: D 0 187, n 1.39 at 5 cGy/min, and D 0 133, n 1.73 at 116 cGy/min ( p · <.05); and FDCP-1JL26 F7 cl 2: D 0 191, n 1.17 at 5 cGy/min, and D 0 150, n 1.31 at 116 cGy/min [ p < .05]). Thus, some hematopoietic progenitor cell lines are induced by GM-CSF to grow after irradiation at low-dose-rate similar to the growth of clonal malignant cell lines. The data may have implications for the radiation biology of normal hematopoietic progenitor cells in two circumstances: (a) selective survival of GM-CSF responsive cells after total body irradiation, and (b) selective survival of some hematopoietic progenitors in vivo during clinical recombinant GM-CSF infusion.