Figure 8. Schematic of radiation-induced alterations in iron handling following total body irradiation.

Following exposure to lethal levels of total body irradiation, there is a depletion of ironcarrying RBC and reticulocytes due to radiation-induced hemolysis, resulting in increased levels of iron Fe²⁺ and Fe³⁺ in the serum. Our data indicate that Fe³⁺ levels increase in the bone marrow and liver, detectable by Prussian blue staining. The changes in iron in the serum result in biphasic regulation of hepcidin in the liver, with ~2.5 fold increase within 7 days post-irradiation, which can suppress iron transfer from enterocytes and macrophages. At the same time, there is increased expression of iron handling proteins in the bone marrow, including proteins for iron uptake, transport, and storage.