Soderberg L S, Barnett J B, Baker M L, Salari H, Sorenson J R
Department of Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock 72205.
Exp Hematol. 1990 Aug;18(7):801-5.
We have previously reported that copper(II)2(3,5-diisopropylsalicylate)4 (Cu-DIPS), administered 3 h before exposure to lethal irradiation, significantly increased the survival rate of mice. Agents that can improve recovery from irradiation are of particular importance for accidental radiation exposure if they are effective when given after exposure. In the present study, we showed that Cu-DIPS had radiation recovery activity when administered subsequent to radiation exposure. Mice were exposed to 800 cGy irradiation and 3 h later injected with vehicle or 20, 40, or 60 mumol/kg Cu-DIPS. The 30-day survival rate was significantly increased at all doses of Cu-DIPS tested. Survival increased from 47% for vehicle-treated mice to 78% (p less than 0.001) for mice treated with 40 mumol/kg. The recovery of hemopoietic activity was assessed in similarly treated mice 14 and 24 days after irradiation. The postirradiation Cu-DIPS treatment significantly increased spleen weights, bone marrow cellularity, and hemopoietic activity in the spleen and bone marrow compared to vehicle-treated controls. Enhanced recovery of hemopoietic activity included both committed progenitor granulocyte-macrophage colony-forming units (GM-CFU) and more primitive stem cells (endogenous spleen colony-forming units, CFU-Se). The number of CFU-Se at 14 days, the number of bone marrow GM-CFU at 24 days, and bone marrow cellularity at 24 days appear to be better predictors of survival rates than other parameters.
我们之前报道过,在暴露于致死性辐射前3小时给予二(3,5-二异丙基水杨酸)铜(II)4(Cu-DIPS),可显著提高小鼠的存活率。对于意外辐射暴露而言,如果在暴露后给予有效的辐射恢复剂,那么这类药物就尤为重要。在本研究中,我们发现辐射暴露后给予Cu-DIPS具有辐射恢复活性。将小鼠暴露于800 cGy辐射下,3小时后注射溶剂或20、40或60 μmol/kg的Cu-DIPS。所有测试剂量的Cu-DIPS均显著提高了30天存活率。存活率从溶剂处理组小鼠的47%提高到40 μmol/kg处理组小鼠的78%(p < 0.001)。在辐射后14天和24天,对接受类似处理的小鼠的造血活性恢复情况进行评估。与溶剂处理的对照组相比,辐射后给予Cu-DIPS治疗显著增加了脾脏重量、骨髓细胞密度以及脾脏和骨髓中的造血活性。造血活性的增强包括定向祖细胞粒细胞-巨噬细胞集落形成单位(GM-CFU)和更原始的干细胞(内源性脾脏集落形成单位,CFU-Se)。14天时CFU-Se的数量、24天时骨髓GM-CFU的数量以及24天时骨髓细胞密度似乎比其他参数更能预测存活率。