Abstract
Purpose: To study whether radiation-induced bleeding in the bone marrow induced iron accumulation, and subsequently caused ferroptosis in granulocyte-macrophage hematopoietic progenitor cells.
Materials and methods: Male mice were subjected to different doses (0, 4, 8, or 10 Gy) of gamma radiation from a 137Cs source. The changes in iron metabolism or ferroptosis-related parameters of irradiated bone marrow were accessed with biochemical, histopathological, and antibody methods. Hematocytes were detected with a hematology analyzer. The counts of granulocyte-macrophage hematopoietic progenitor cells were measured with the granulocyte-macrophage colony-forming unit.
Results: Iron accumulation occurred in the bone marrow, which caused by radiation-induced hemorrhage. The iron accumulation triggered an iron regulatory protein-ferroportin 1 axis to increase serum iron levels. Using LDN193189, radiation-induced iron accumulation was demonstrated to decrease white blood cell counts at least partly through a decrease in the counts of granulocyte-macrophage hematopoietic progenitor cells. The reduction in the counts of granulocyte-macrophage hematopoietic progenitor cells was subsequently demonstrated to attribute to ferroptosis with the use of ferroptosis inhibitors and through the detection of ferroptosis related-parameters. The survival rate of irradiated mice was improved using Ferrostatin-1 or LDN193189.
Conclusions: These findings suggest that radiation-induced hemorrhage in the bone marrow causes ferroptosis in granulocyte-macrophage hematopoietic progenitor cells, and anti-ferroptosis has the potential to be a radioprotective strategy to ameliorate radiation-induced hematopoietic injury.
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The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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Xiaohong Zhang
Xiaohong Zhang, PhD. She is a senior experimentalist in the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics. Her research interests are in the areas of radiation biology and biodosimetry.
Xueshuang Xing
Xueshuang Xing, MD. She is a postgraduate in the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics. Her research interests are in the area of radiation biology.
Huiwen Liu
Huiwen Liu, MD. She is a postgraduate in the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics. Her research interests are in the area of radiation biology.
Jundong Feng
Jundong Feng, PhD. She is an associate professor in the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics. Her research interests are in the area of space radiation protection.
Mengxin Tian
Mengxin Tian, MD. She is a postgraduate in the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics. Her research interests are in the area of radiation biology.
Shuquan Chang
Shuquan Chang, PhD. He is the head of the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics. His research interests are in the area of radiation protection.
Peidang Liu
Peidang Liu, PhD. He is an associate professor of the Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University. His research interests are in the areas of radiation biology and radiotherapy.
Haiqian Zhang
Haiqian Zhang, PhD. He is a professor in the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics. His research interests are in the area of radiation protection.