Rasey J S, Nelson N J, Mahler P, Anderson K, Krohn K A, Menard T
Radiat Res. 1984 Mar;97(3):598-607.
The ability of WR-2721 to protect mice against two modes of death following whole-body radiation with 137Cs gamma rays or d(22)+Be neutrons was examined. For single fractions, 400 mg/kg WR-2721 was administered prior to irradiation. In two-fraction exposures, the dose was 275 mg/kg given prior to each fraction. Dose modification factors (DMFs) were calculated as ratios of LD50 values. For single fractions of gamma rays, the DMF was 1.74 for the LD50/7 end point and for LD50/30, the DMF for single fractions was 2.25. For two fractions 3 hr apart, it was 1.88. For single fractions of cyclotron neutrons, the DMF was 1.32 for LD50/7. Measured with the LD50/30 end point, the DMF for single neutron doses was 1.41 and for two fractions, 1.19. Substantial radioprotection of bone marrow and intestinal epithelium against cyclotron neutrons was seen in these investigations. Biodistribution studies were done following ip injection of 35S-labeled WR-2721 into C3H mice bearing RIF-1 tumors. Blood levels peaked at 10 min after injection and declined thereafter. Most normal tissues achieved maximum levels of 35S at 30 to 60 min postinjection and high concentrations were retained in most tissues for up to 2 hr. Assuming that all 35S is in parent compound or dephosphorylated radioprotective metabolites, the concentration of protector (milligram per gram tissue) in various organs at 30 min postinjection ranked as follows: kidney greater than submandibular gland much greater than liver = lung greater than gut greater than heart much greater than blood greater than skin greater than tumor greater than brain. High levels of 35S were achieved and retention times were long in certain normal tissues which respond at early or late times postradiation and may be dose limiting in radiotherapy: kidney, liver, salivary gland, and lung. These combined observations suggest that there is potential for protecting dose-limiting, late-responding normal tissue in the radiotherapy of human cancer with both neutrons and conventional radiotherapy.
研究了WR-2721保护小鼠免受137Csγ射线或d(22)+Be中子全身照射后两种死亡模式影响的能力。对于单次照射，在照射前给予400mg/kg的WR-2721。在两次照射中，每次照射前的剂量为275mg/kg。剂量修正因子（DMF）以LD50值的比值计算。对于单次γ射线照射，LD50/7终点的DMF为1.74，对于LD50/30，单次照射的DMF为2.25。对于间隔3小时的两次照射，DMF为1.88。对于回旋加速器中子的单次照射，LD50/7的DMF为1.32。以LD50/30终点测量，单次中子剂量的DMF为1.41，两次照射的DMF为1.19。在这些研究中观察到骨髓和肠上皮对回旋加速器中子有显著的辐射防护作用。在给携带RIF-1肿瘤的C3H小鼠腹腔注射35S标记的WR-2721后进行了生物分布研究。血液水平在注射后10分钟达到峰值，随后下降。大多数正常组织在注射后30至60分钟达到35S的最高水平，并且在大多数组织中高浓度持续长达2小时。假设所有35S都存在于母体化合物或去磷酸化的辐射防护代谢物中，注射后30分钟时各器官中保护剂（毫克/克组织）的浓度排名如下：肾脏＞颌下腺＞＞肝脏 = 肺＞肠道＞心脏＞＞血液＞皮肤＞肿瘤＞大脑。在某些辐射后早期或晚期有反应且可能在放射治疗中限制剂量的正常组织中达到了高水平的35S且保留时间长：肾脏、肝脏、唾液腺和肺。这些综合观察结果表明，在人类癌症的中子放疗和传统放疗中，保护剂量限制的、晚期反应的正常组织具有潜力。
