Patchen M L, MacVittie T J, Weiss J F
Armed Forces Radiobiology Research Institute, Bethesda, MD 20814-5145.
Int J Radiat Oncol Biol Phys. 1990 May;18(5):1069-75. doi: 10.1016/0360-3016(90)90442-m.
Glucan, WR-2721, and selenium, three agents with distinct radioprotective mechanisms, were evaluated in C3H/HeN mice for survival-enhancing and hemopoietic-regenerating effects when administered alone or in combinations before exposure to 60Co radiation. At LD50/30 radiation doses (radiation doses lethal for 50% of mice within 30 days postexposure), dose reduction factors of 1.21, 1.02, 1.37, 1.51, and 1.66 were obtained following glucan (75 mg/kg i.v., -20 hr), selenium (0.8 mg/kg, i.p., -20 hr), WR-2721 (200 mg/kg, i.p., -30 min), glucan + WR-2721, and glucan + selenium + WR-2721 treatments, respectively. All treatments increased numbers of hemopoietic stem cells as measured by the day 12 endogenous spleen colony-forming unit (E-CFU) assay; the most significant E-CFU effects, however, were observed following glucan + WR-2721 and glucan + selenium + WR-2721 treatments. Combined modality treatments were also more effective than single-agent treatments at accelerating bone marrow and splenic granulocyte-macrophage colony-forming cell (GM-CFC) regeneration. These results demonstrate the value of multiple-agent radioprotectants.
葡聚糖、WR-2721和硒是三种具有不同辐射防护机制的药剂，在C3H/HeN小鼠中，于暴露于60Co辐射前单独或联合给药时，评估它们对提高存活率和促进造血再生的作用。在LD50/30辐射剂量（暴露后30天内使50%小鼠致死的辐射剂量）下，葡聚糖（静脉注射75 mg/kg，-20小时）、硒（腹腔注射0.8 mg/kg，-20小时）、WR-2721（腹腔注射200 mg/kg，-30分钟）、葡聚糖+WR-2721以及葡聚糖+硒+WR-2721处理后，剂量降低因子分别为1.21、1.02、1.37、1.51和1.66。通过第12天内源性脾集落形成单位（E-CFU）测定法测量，所有处理均增加了造血干细胞数量；然而，在葡聚糖+WR-2721和葡聚糖+硒+WR-2721处理后观察到最显著的E-CFU效应。联合治疗在加速骨髓和脾脏粒细胞-巨噬细胞集落形成细胞（GM-CFC）再生方面也比单药治疗更有效。这些结果证明了多药剂辐射防护剂的价值。
