Protection of mice against X-ray injuries by the post-irradiation administration of guanosine and inosine.
OBJECTIVE
To examine the radioprotective action of guanosine (Guo) and inosine (Ino) administered to mice after irradiation with X-rays.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Guo and Ino introduced shortly after irradiation reduce leukopenia and thrombocytopenia and offer promise as therapeutic agents for treatment of radiation injuries.
Gudkov
Sergey V
SV
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region.
Gudkova
Olga Y
OY
Chernikov
Anatoly V
AV
Bruskov
Vadim I
VI
D000818:Animals; D001772:Blood Cell Count; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006151:Guanosine / Q000494:pharmacology*; D007288:Inosine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014965:X-Rays
D011837:Radiation-Protective Agents; D006151:Guanosine; D016179:Granulocyte Colony-Stimulating Factor; D007288:Inosine