Palmer T E, Glaza S M, Dickie B C, Weltman R H, Greenspun K S
Toxicol Pathol. 1985;13(1):58-65. doi: 10.1177/019262338501300108.
WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, is used extensively to protect normal cells during the irradiation of neoplastic cells. Dose levels for human radiotherapy are based on results obtained from laboratory animal lethality and toxicity studies. WR-2721 was administered intravenously to CDF1 mice and beagle dogs. Single dose lethality studies in mice showed the average 1/10 of the lethal dose, the median lethal dose and 9/10 the lethal dose to be 508 (1523 mg/m2), 589 (1766 mg/m2), and 682 mg/kg (2047 mg/m2), respectively. The lethal dose for female mice was lower than that for males. The 1/10 lethal dose in mice was slightly toxic to dogs; 1/10 of that dose was nontoxic. The lethal dose for dogs (6000 mg/m2) was higher than that for mice (2000 mg/m2). Clinical signs of toxicosis in the single-dose mouse toxicity study were evident in the 1st week following treatment and declined during the recovery period; signs of toxicosis were transient in dogs. Acute drug-induced pathologic changes included elevated BUN and SGOT levels, lymphoid necrosis, and renal tubular degeneration in mice. These changes were evident in the 1st week following treatment, but had dissipated by study termination. Generalized vascular changes (congestion, hemorrhage, and edema) and renal tubular degeneration occurred in treated dogs that had died or were killed moribund 7 days postinjection. These findings indicate sex-dependent and interspecies variation in the toxicity of WR-2721 with acute, but reversible, pathologic changes.
WR-2721，即S-2-(3-氨丙基氨基)乙硫代磷酸，在肿瘤细胞放疗期间被广泛用于保护正常细胞。人类放射治疗的剂量水平是基于从实验动物致死率和毒性研究中获得的结果。对CDF1小鼠和比格犬静脉注射WR-2721。小鼠单剂量致死率研究表明，平均致死剂量的1/10、半数致死剂量和9/10致死剂量分别为508（1523毫克/平方米）、589（1766毫克/平方米）和682毫克/千克（2047毫克/平方米）。雌性小鼠的致死剂量低于雄性小鼠。小鼠的1/10致死剂量对犬有轻微毒性；该剂量的1/10无毒。犬的致死剂量（6000毫克/平方米）高于小鼠（2000毫克/平方米）。单剂量小鼠毒性研究中的中毒临床症状在治疗后的第1周明显，在恢复期下降；犬的中毒症状是短暂的。急性药物诱导的病理变化包括小鼠血尿素氮和谷草转氨酶水平升高、淋巴样坏死和肾小管变性。这些变化在治疗后的第1周明显，但在研究结束时已消失。在注射后7天死亡或濒死时被处死的治疗犬中出现了全身性血管变化（充血、出血和水肿）和肾小管变性。这些发现表明WR-2721的毒性存在性别依赖性和种间差异，伴有急性但可逆的病理变化。
