Biological Effect of Recombinant Human Granulocytes Colony-Stimulating Factor on X-Ray Irradiated Mice with Bone Marrow Transplantation

Human granulocyte colony-stimulating factor (hG-CSF) is one of the hematopoietic factors that controls the differentiation of pluripotent stem cells in many types of blood cells during hematopoiesis. It also plays a key role in the stimulation of proliferation and differentiation of several types of blood cells including granulocytes and macrophages. This study examined the effects of recombinant hG-CSF (rhG-CSF) on the recovery of peripheral neutrophil number, DNA damage of peripheral blood and the survival rate of mice that received whole-body X-ray irradiation. rhG-CSFs were prepared by replacing the respective Met 1 7 with Ser 1 7 , Ala 1 7 , and Gly 1 7 . [Ser 1 7 ] G-CSF, [Ala 1 7 ] G-CSF and [Gly 1 7 ] G-CSF (10 μg/kg) each were administered subcutaneously to X-ray-irradiated mice for 21 days after the bone marrow transplantation. Treatment of rhGCSF increased the neutrophil differentiation significantly. Peripheral neutrophil number and the ratio of myloid to erythoid in the bone marrow gradually recovered to the normal level from the 13th day. [Ser 1 7 ] G-CSF-treated group was significantly different compared with the vehicle-treated group, and [Ala 1 7 ] G-CSF and [Ser 1 7 ] G-CSF-treated groups showed the highest levels on the 17th and 21st day, respectively. The mortality of [Ser 1 7 ] G-CSF-treated group was the lowest compared to approximately 30% death rate of the vehicle-treated group. Moreover, on the average, micronucleus (MN) frequencies of all treated groups tended to decrease gradually from the 9th to the 25th day. MN frequencies of [Ser 1 7 ] G-CSF and [Ala 1 7 ] G-CSF-treated groups were significantly lower than those of the vehicle control group (p < 0.05) from the 13th day. This observation suggests that methionyl-free rhG-CSF might have a protective role in severely irradiated mice and application of [Ser 1 7 ] G-CSF hastened the recovery of leukocytes and neutrophils in peripheral blood.