Biological effect of recombinant human granulocytes colony- stimulating factor on X-ray irradiated mice with bone marrow transplantation

Abstract

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 Met17 with Ser17, Ala17, and Gly17. [Ser17] G-CSF, [Ala17] G-CSF and [Gly17] G-CSF (10 μg/kg) each were administered subcutaneously to X-ray-irradiated mice for 21 days after the bone marrow transplantation. Treatment of rhG-CSF 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. [Ser17] G-CSF-treated group was significantly different compared with the vehicle-treated group, and [Ala17] G-CSF and [Ser17] G-CSF-treated groups showed the highest levels on the 17th and 21st day, respectively. The mortality of [Ser17] 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 [Ser17] G-CSF and [Ala17] 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 [Ser17] G-CSF hastened the recovery of leukocytes and neutrophils in peripheral blood.