Sodicoff M, Ziskin M C, Conger A D
Radiat Res. 1986 Jul;107(1):49-57.
The radioprotector WR-2721 has been shown to radioprotect all tissues studied except the central nervous system. However, it has not yet been used to radioprotect the fetus. In this study we determined that [14C]WR-2721 injected into pregnant rats quickly passed the placenta and was concentrated by the fetus. In addition, we evaluated the toxicity of WR-2721 (2.5-600 mg/kg) to pregnant rats and their fetuses during the period of major organogenesis at Days 9, 11, and 14 postconception. Pregnant animals were only slightly more (10%) sensitive (LD50, 580 mg/kg) to WR-2721 than nonpregnant cohort animals (LD50, 640 mg/kg). At concentrations of 50 mg/kg or less there was a small but statistically significant increase in fetal deaths, while at doses greater than 300 mg/kg a larger degree of fetal mortality occurred. Maximal fetal weight loss, to about 84% of control, was found at 500 mg/kg. No changes in head dimensions or gross malformations of the surviving fetuses were detected at any time or concentration. Of all the parameters measured in this study none demonstrated a predilection for any specific period of major organogenesis. The results of this study indicate that while WR-2721 demonstrates a dose-related embryotoxicity it is not teratogenic.
辐射防护剂WR-2721已被证明可对除中枢神经系统外的所有研究组织起到辐射防护作用。然而，它尚未被用于对胎儿进行辐射防护。在本研究中，我们确定向怀孕大鼠注射[14C]WR-2721后，其可迅速通过胎盘并在胎儿体内富集。此外，我们评估了WR-2721（2.5 - 600毫克/千克）在受孕后第9、11和14天主要器官形成期对怀孕大鼠及其胎儿的毒性。怀孕动物对WR-2721的敏感性仅略高于（10%）未怀孕的同组动物（半数致死量分别为580毫克/千克和640毫克/千克）。当浓度为50毫克/千克或更低时，胎儿死亡有少量但具有统计学意义的增加，而当剂量大于300毫克/千克时，胎儿死亡率更高。在500毫克/千克时发现胎儿体重最大降幅，约为对照组的84%。在任何时间或浓度下，均未检测到存活胎儿的头部尺寸变化或明显畸形。在本研究测量的所有参数中，没有任何一个显示出对主要器官形成的任何特定时期有偏好。本研究结果表明，虽然WR-2721表现出剂量相关的胚胎毒性，但它没有致畸性。
