Gudkov Sergey V, Gudkova Olga Y, Chernikov Anatoly V, Bruskov Vadim I
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region.
Int J Radiat Biol. 2009 Feb;85(2):116-25. doi: 10.1080/09553000802641144.
To examine the radioprotective action of guanosine (Guo) and inosine (Ino) administered to mice after irradiation with X-rays.
Survival of mice exposed to lethal and sublethal doses of X-rays was studied. Peripheral blood cells were counted using a light microscope. The damage to bone marrow cells was assessed by micronucleus (MN) test. Damage and repair of DNA in blood leukocytes were estimated using the comet assay.
Mice injected intraperitoneally (i.p.) with Guo or Ino ( approximately 30 microg g(-1), i.e., approximately 0.6 mg per 20-g mouse) 15 min after acute whole-body irradiation with 7 Gy recovered from X-ray injury. On the 30th day after irradiation, 50 and 40% of mice injected with Guo and Ino, respectively, remained alive. The dose reduction factor (DRF) was 1.23 for Guo and 1.15 for Ino. The protective effect gradually decreased as the time interval between the irradiation and injection was increased to 3, 5, 8 h. Guo and Ino facilitated the restoration of peripheral blood cell counts. These compounds protected bone marrow cells from damage and normalized erythropoiesis. Guo and Ino contributed to a more rapid and complete repair of DNA in mouse leukocytes irradiated both in vitro and in vivo.
Guo and Ino introduced shortly after irradiation reduce leukopenia and thrombocytopenia and offer promise as therapeutic agents for treatment of radiation injuries.
研究X射线照射后给予小鼠鸟苷(Guo)和肌苷(Ino)的辐射防护作用。
研究暴露于致死和亚致死剂量X射线的小鼠的存活率。使用光学显微镜对外周血细胞进行计数。通过微核(MN)试验评估骨髓细胞的损伤。使用彗星试验估计血液白细胞中DNA的损伤和修复情况。
急性全身7 Gy照射后15分钟腹腔注射Guo或Ino(约30 μg g⁻¹,即每20 g小鼠约0.6 mg)的小鼠从X射线损伤中恢复。照射后第30天,注射Guo和Ino的小鼠分别有50%和40%存活。Guo的剂量降低因子(DRF)为1.23,Ino为1.15。随着照射与注射之间的时间间隔增加到3、5、8小时,保护作用逐渐降低。Guo和Ino促进外周血细胞计数的恢复。这些化合物保护骨髓细胞免受损伤并使红细胞生成正常化。Guo和Ino有助于体外和体内照射的小鼠白细胞中DNA更快、更完全地修复。
照射后不久给予的Guo和Ino可减轻白细胞减少和血小板减少,并有望作为治疗辐射损伤的治疗剂。