title: 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 greater than or equal to 50 cell colonies. The cell lines demonstrated similar radiosensitivity and lack of a detectable dose-rate effect when grown in IL-3 (FDCP-1JL26: D0 154, n 1.05 at 5 cGy/min, and D0 138, n 1.16 at 116 cGy/min; bg/bg d64: D0 95.7, n 1.16 at 5 cGy/min, and D0 97.7 n .993 at 116 cGy/min; B6SUtA: D0 101, n 1.29 at 5 cGy/min, D0 100, n 1.27 at 116 cGy/min; and cell line 32D cl 3: D0 123, n 1.65 at 5 cGy/min, and D0 126, n 1.17 at 116 cGy/min). In contrast, FDCP-1JL26 cells demonstrated a significant relative radioresistance at low-dose-rate when grown in recombinant GM-CSF, (D0 217, n 1.27 at 5 cGy/min, D0 138, n 1.34 at 116 cGy/min, p less than .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 FDCP-1JL26 demonstrated a significant increase in radioresistance at low-dose-rate (B6SUtA EL4JL: D0 187, n 1.39 at 5 cGy/min, and D0 133, n 1.73 at 116 cGy/min (p. less than .05); and FDCP-1JL26 F7 cl 2: D0 191, n 1.17 at 5 cGy/min, and D0 150, n 1.31 at 116 cGy/min [p less than .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.
authors.affiliation: Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester 01655.
authors.forename: T J
authors.initials: TJ
authors.lastname: FitzGerald
authors.forename: S
authors.initials: S
authors.lastname: Henault
authors.forename: M A
authors.initials: MA
authors.lastname: Santucci
authors.forename: P
authors.initials: P
authors.lastname: Anklesaria
authors.forename: S
authors.initials: S
authors.lastname: Zak
authors.forename: K
authors.initials: K
authors.lastname: Kase
authors.forename: N
authors.initials: N
authors.lastname: Farber
authors.forename: J H
authors.initials: JH
authors.lastname: Pierce
authors.forename: A
authors.initials: A
authors.lastname: Ohara
authors.forename: J S
authors.initials: JS
authors.lastname: Greenberger
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D002588:Cesium Radioisotopes; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D011836:Radiation Tolerance; D011994:Recombinant Proteins; D013268:Stimulation, Chemical
chemical_list: D002588:Cesium Radioisotopes; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor