Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
In Vivo. 2011 May-Jun;25(3):315-23.
BACKGROUND/AIM: Total-body irradiation (TBI) doses in the range of 2-8 Gy are associated with a drop in peripheral blood counts, decreased bone marrow cellularity, and hematopoietic syndrome. Radiation mitigators must be safe for individuals likely to recover spontaneously.
Female C57BL/6HNsd mice exposed to 9.0 and 9.15 Gy TBI, received intraperitoneal (10 mg/kg) JP4-039, a novel radiation mitigator, 24 hours after irradiation and were followed for hematopoietic recovery.
Irradiated mice showed reduced peripheral blood lymphocytes and neutrophils and bone marrow cellularity at day 5. Serum electrolytes, liver and renal function tests showed no deleterious effect of JP4-039-after irradiation, and no reduction in survival compared to irradiated controls. Marrow recovery measured as cellularity, and hematopoietic colony-forming cells including primitive granulocyte-erythroid-megakaryocyte-monocytes (GEMM), reached pre-irradiation levels by day 30 in JP4-039 treated groups. Mice receiving single or multiple administrations of JP4-039 showed an early return of CFU-GEMM.
JP4-039 (GS-Nitroxide) is a safe radiation mitigator in mice warranting studies in larger animals and potentially a Phase I Clinical Trial.
背景/目的：2-8 Gy 范围内的全身照射（TBI）会导致外周血计数下降、骨髓细胞减少和造血综合征。辐射缓解剂必须对可能自发恢复的个体是安全的。
接受 9.0 和 9.15 Gy TBI 的雌性 C57BL/6HNsd 小鼠在照射后 24 小时内接受腹腔内（10 mg/kg）JP4-039，一种新型辐射缓解剂，并进行造血恢复的随访。
照射后的小鼠在第 5 天表现出外周血淋巴细胞和中性粒细胞减少以及骨髓细胞减少。血清电解质、肝功能和肾功能检查显示 JP4-039 照射后没有不良影响，与照射对照组相比，生存率没有降低。骨髓恢复的测量指标包括细胞计数和造血集落形成细胞，包括原始粒细胞-红细胞-巨核细胞-单核细胞（GEMM），在 JP4-039 治疗组中在第 30 天达到照射前的水平。单次或多次接受 JP4-039 治疗的小鼠显示 CFU-GEMM 早期恢复。
JP4-039（GS-Nitroxide）是一种安全的小鼠辐射缓解剂，值得在较大动物中进行研究，并有可能进行 I 期临床试验。
