STUDY OF PROTECTIVE EFFECTS OF 5,6,7,8-TETRA-HYDRONEOPTERIN AGAINST X-RAY RADIATION INJURY

研究了5，6，7，8-四氢新蝶呤（NPH-4）对小鼠辐射损伤的保护作用。（C57 BL/6 x A/J）F1（B6 A）小鼠接受200、400、700或800 cGy X射线的单次全身照射剂量。照射前、后10分钟及照射后6小时分别腹腔注射NPH-4（30 mg/kg体重）或BPS。所有接受800 cGy辐射+ PBS的小鼠在治疗后8至11天死亡。相比之下，那些也接受NPH-4的患者的生存时间显着延长，40%的患者存活超过5个月。照射后第5天，胸腺细胞和脾细胞的总数急剧减少，与辐射剂量一致。在NPH-4处理中，存活率显著提高。在NPH-4处理的小鼠中，伴刀豆球蛋白A（Con A）或脂多糖（LPS）刺激的小鼠中的脾细胞增殖也更大。800 cGy + NPH-4治疗5个月后，存活小鼠对ConA、LPS、同种异体小鼠和渗漏红细胞（SRBC）的免疫应答基本恢复到正常小鼠水平。这些结果表明，NPH-4在预防辐射损伤中具有重要作用。总之，NPH-4可能用作治疗剂，用于治疗以活性氧作为潜在致病因素的疾病，例如辐射后损伤。特别是，NPH-4可能与放射疗法联合应用于血管形成不良的人类癌症，如某些胰腺癌。

The protective effects of 5,6,7,8-tetrahydroneopterin (NPH-4) against radiation injury in mice was studied. (C57BL/6 x A/J) F1 (B6A) mice of received a single whole-body irradiation dose of 200,400,700 or 800 cGy X-rays. NPH-4 (30mg/kg body weight) or BPS were injected intraperitoneally into irradiated mice 10 minutes before and after the irradiation and again after 6 hours. All mice which received the 800 cGy radiation + PBS died between 8 to 11 days after the treatment. In contrast, those that also received NPH-4 demonstrated a significantly prolonged survival time and 40% lived more than 5 months. Total numbers of thymocytes and spleen cells on day 5 post-irradiation were dramatically reduced in line with the radiation dose. The survival was significantly enhanced by in NPH-4 treated. Proliferation of spleen cells in mice stimulated by concanavilin A (Con A) or lipopolysaccharide (LPS) was also greater in NPH-4 treated mice. The immune response of survivors, 5 months after 800 cGy + NPH-4 treatments, against Con A,LPS,allogeneic mouse, and seep red blood cells (SRBC) had essentially ecovered to the levels of normal mice. These results indicate that NPH-4 had an important role in preventing radiation injury.In conclusion, NPH-4 may be useful as a therapeutic agent against diseases in which active oxygen species act as potent pathogenic factors, such as with post-radiation injury. In particular, NPH-4 might findapplication in combination with radiation therapy for human cancers with poor blood vessel formation such as some pancreatic carcinomas.