Bradfield Dmitry T, Slaven John E, Rittase W Bradley, Rusnak Milan, Symes Aviva J, Brehm Grace V, Muir Jeannie M, Lee Sang-Ho, Anderson Joseph A, Day Regina M
Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
PLoS One. 2025 May 29;20(5):e0324361. doi: 10.1371/journal.pone.0324361. eCollection 2025.
Different tissues exhibit differential sensitivity to ionizing radiation exposure and display different time courses of pathologies that are not well understood. Ionizing radiation causes hemolysis of red blood cells, causing the release of iron that is taken up by a variety of tissues. The increased iron has been associated with altered expression of iron binding proteins and, in some cases, markers of ferroptosis. Here we examined the time course of iron uptake in murine liver following 60Co total body irradiation (TBI) at 7.9 Gy (LD90/30) and 6.85 Gy (LD0/30). 7.9 Gy induced hydropic degeneration, micro-vesicular steatosis, and inflammatory cell infiltration, whereas at 6.85 Gy the livers displayed only inflammatory cell infiltration. In both cases, iron levels increased significantly, maximal at ~21 days post-TBI. Increased iron was associated with altered expression of ferritin, heme oxygenase, an enzyme required for iron recycling, and the pro-inflammatory cytokine serum amyloid A, maximal ~16-21 days. 7.9 Gy induced liver caspase-3 activation consistent with apoptosis. In contrast, 6.85 Gy induced markers of ferroptosis but not of apoptosis. Our data indicate that iron is deposited in the liver at a delayed time point following radiation and is associated with increased ferritin, HO-1, and inflammatory cytokine production.
不同组织对电离辐射暴露表现出不同的敏感性，并呈现出尚不为人所熟知的不同病理时间进程。电离辐射会导致红细胞溶血，致使铁释放出来并被多种组织摄取。铁含量增加与铁结合蛋白表达的改变相关，在某些情况下，还与铁死亡标志物有关。在此，我们研究了在7.9 Gy（LD90/30）和6.85 Gy（LD0/30）剂量的60Co全身照射（TBI）后，小鼠肝脏中铁摄取的时间进程。7.9 Gy诱导了细胞水肿性变性、微泡性脂肪变性和炎性细胞浸润，而在6.85 Gy时，肝脏仅表现出炎性细胞浸润。在这两种情况下，铁水平均显著升高，在TBI后约21天达到峰值。铁含量增加与铁蛋白、血红素加氧酶（铁循环所需的一种酶）以及促炎细胞因子血清淀粉样蛋白A的表达改变相关，峰值出现在约16 - 21天。7.9 Gy诱导肝脏半胱天冬酶 - 3激活，与细胞凋亡一致。相比之下，6.85 Gy诱导了铁死亡标志物而非细胞凋亡标志物。我们的数据表明，铁在辐射后的延迟时间点沉积在肝脏中，并与铁蛋白、HO - 1和炎性细胞因子产生增加有关。
