Dose-time Characteristics of Acute Hematopoietic and Immune Injury Induced by Whole-body 60Co Gamma-irradiation in Mice
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Abstract
To systematically characterize the dose-dependent and time-dependent features of acute hematopoietic and immune injury induced by total-body irradiation with 60Co gamma rays, BALB/c mice were exposed to 0, 1, 2, 4, or 8 Gy and examined on days 1, 3, and 7 after irradiation. Peripheral blood parameters, organ indices, and flow-cytometric changes in apoptosis and immune cell subsets in bone marrow and thymus were analyzed. The results show that the severity of acute injury increases with radiation dose, while recovery becomes progressively limited at higher doses. White blood cells and granulocytes decrease rapidly after irradiation and display clear dose-response relationships at all observed time points. The 1 Gy group shows a recovery trend by day 7, whereas the 2-8 Gy groups remain at low levels, indicating that restoration of peripheral blood cells is dose-limited during the acute phase. The thymus is the most radiosensitive target, as reflected by a marked reduction in thymus index after irradiation. Thymocyte apoptosis increases in a dose-dependent manner on days 1 and 3. Further analysis of thymic T-cell subsets shows that the proportion of CD4+CD8+ double-positive (DP) cells decreases markedly with increasing dose at all time points, with the most prominent suppression in the 4 Gy and 8 Gy groups, indicating that DP cells are highly sensitive to gamma-ray exposure. Bone marrow injury shows an evident stage-dependent pattern. On day 1, the overall proportion of CD45+ cells remains relatively stable, whereas the proportion of CD19+CD3− cells decreases with dose, indicating that early injury is first manifested as changes in cellular composition, especially in the B-lineage-related compartment. By day 3, CD45+ cells begin to decline in the 4 Gy and 8 Gy groups, showing progression from subpopulation alteration to impairment of the overall marrow leukocyte pool. At the same time, the Lin−Sca-1+c-Kit+ (LSK) subset exhibits the most obvious decrease, indicating significant suppression of early hematopoietic stem/progenitor-associated populations. By day 7, differences in marrow subpopulation proportions reduce, but the 4 Gy group still shows a persistently decreased CD45+ proportion and relatively high apoptosis, indicating limited recovery of the overall marrow leukocyte pool. Some rebound is observed in the LSK subset at later time points, but recovery remains incomplete in the higher-dose groups. Overall, acute injury induced by 60Co gamma rays is characterized mainly by suppression of bone marrow hematopoiesis and disturbance of thymic T-cell development. The process shows dose dependence and temporal evolution: The 1 Gy and 2 Gy groups retain partial recovery capacity within the observation period, whereas the 4 Gy and 8 Gy groups exhibit sustained injury and restricted immune reconstruction. These findings provide a relatively systematic description of acute radiation-induced hematopoietic and immune injury across multiple levels, and provide an experimental basis for further studies on early radiation injury assessment and related protective interventions.
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