Gamma radiation suppresses bone marrow primarily because it damages the rapidly dividing cells within the marrow, disrupting their ability to produce blood cells. Bone marrow contains hematopoietic stem cells (HSCs) that constantly divide to replenish red blood cells, white blood cells, and platelets. Gamma radiation, being highly energetic ionizing radiation, penetrates tissues and causes direct DNA damage and oxidative stress in these cells, leading to cell death or malfunction.
At the cellular level, gamma radiation induces mitochondrial dysfunction in bone marrow cells. It disrupts the mitochondrial membrane potential and increases membrane permeability, causing swelling and rupture of mitochondria. This mitochondrial damage leads to the release of mitochondrial DNA into the cytoplasm, which activates inflammatory signaling pathways that exacerbate bone marrow injury. Radiation also promotes oxidative stress through lipid peroxidation, further damaging hematopoietic stem cells and impairing their function. This oxidative damage can trigger apoptosis (programmed cell death) in these critical cells, reducing the marrow’s capacity to regenerate blood cells.
Moreover, gamma radiation affects the bone marrow microenvironment, including the blood vessels and supporting stromal cells, which are essential for maintaining hematopoiesis. Radiation-induced damage to capillary endothelium impairs blood supply and nutrient delivery to the marrow, compounding the suppression of blood cell production. The severity of marrow suppression correlates with the radiation dose, with higher doses causing more profound and longer-lasting neutropenia (low neutrophil count) and pancytopenia (reduction in all blood cell types).
The timeline of radiation effects on bone marrow includes an initial phase of decreased cellularity with edema and hemorrhage, followed by a transient increase in cellularity due to influx from non-irradiated areas, and then a prolonged phase of marrow depletion. Over months, some regeneration may occur, but severe damage can lead to life-threatening immunodeficiency, anemia, and bleeding due to the loss of white cells, red cells, and platelets respectively.
In addition to direct DNA damage, gamma radiation disrupts mitochondrial metabolism, including serine catabolism, which is crucial for cell survival and function. Supplementing certain metabolites like serine has been shown experimentally to reduce radiation-induced hematopoietic suppression, highlighting the metabolic vulnerability of bone marrow cells to radiation.
Overall, gamma radiation suppresses bone marrow by killing or impairing the function of hematopoietic stem and progenitor cells through DNA damage, mitochondrial dysfunction, oxidative stress, and disruption of the marrow microenvironment. This leads to decreased production of blood cells, resulting in immunosuppression, anemia, and bleeding risks that characterize radiation sickness and complicate recovery after exposure.