Pretreatment with granulocyte colony-stimulating factor reduces myelopoiesis in irradiated mice

The purpose of this study was to investigate effects of the treatment prior to irradiation with granulocyte colony-stimulating factor (G-CSF) on hemat opoiesis in B10CBAF(1), mice exposed to a sublethal dose of 6.5 Gy of Co-60 gamma radiation. G-CSF was administered in a 4-day regimen (3 mu g/day); i rradiation followed 3 h after the last injection of G-CSF. Such a treatment was found to stimulate granulopoiesis, as shown by increased counts of gra nulocyte-macrophage progenitor cells (GM-CFC) and of granulocytic cells in the femoral marrow and spleen at the time of irradiation. However, postirra diation counts of GM-CFC and granulocytic cells in the marrow of mice pretr eated with G-CSF were reduced up to day 18 after irradiation, Interestingly , the D-0 values for marrow GM-CFC determined 1 h after in vivo irradiation were 1.98 Gy for controls and 2.47 Gy for mice pretreated with G-CSF, indi cating a decreased radiosensitivity of these cells after drug treatment. Th e inhibitory effects of the pretreatment with G-CSF on the postirradiation granulopoiesis could be attributed to the phenomenon of "rebound quiescence " which can occur after cessation of the treatment with growth factors. Pos tirradiation recovery of erythropoiesis in the spleen of mice pretreated wi th G-CSF exhibited a dramatic increase and compensated for the decreased er ythropoiesis in the marrow at the time of irradiation. This complexity of t he hematopoietic response should be taken into account when administering G -CSF in preirradiation regimens. (C) 1999 by Radiation Research Society.