Accession Number : ADA562661


Title :   Amelioration of Radiation-Induced Hematopoietic and Gastrointestinal Damage by Ex-RAD (trademark) in Mice


Descriptive Note : Journal article


Corporate Author : UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD


Personal Author(s) : Ghosh, Sanchita P ; Kulkarni, Shilpa ; Perkins, Michael W ; Hieber, Kevin ; Pessu, Roli L ; Gambles, Kristen ; Maniar, Manoj ; Kao, Tzu-Cheg ; Seed, Thomas M ; Kumar, K S


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a562661.pdf


Report Date : 06 Jun 2012


Pagination or Media Count : 12


Abstract : The aim of the present study was to assess recovery from hematopoietic and gastrointestinal damage by Ex-RAD , also known as ON01210.Na (4-carboxystyryl-4-chlorobenzylsulfone, sodium salt), after total body radiation. In our previous study, we reported that Ex-RAD, a small-molecule radioprotectant, enhances survival of mice exposed to gamma radiation, and prevents radiation-induced apoptosis as measured by the inhibition of radiation-induced protein 53 (p53) expression in cultured cells. We have expanded this study to determine best effective dose, dose-reduction factor (DRF), hematological and gastrointestinal protection, and in vivo inhibition of p53 signaling. A total of 500 mg/kg of Ex-RAD administered at 24 h and 15 min before radiation resulted in a DRF of 1.16. Ex-RAD ameliorated radiation-induced hematopoietic damage as monitored by the accelerated recovery of peripheral blood cells, and protection of granulocyte macrophage colony-forming units (GM-CFU) in bone marrow. Western blot analysis on spleen indicated that Ex- RAD treatment inhibited p53 phosphorylation. Ex-RAD treatment reduces terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay (TUNEL)-positive cells in jejunum compared with vehicletreated mice after radiation injury. Finally, Ex-RAD preserved intestinal crypt cells compared with the vehicle control at 13 and 14 Gy. The results demonstrated that Ex-RAD ameliorates radiation-induced peripheral blood cell depletion, promotes bone marrow recovery, reduces p53 signaling in spleen and protects intestine from radiation injury.


Descriptors :   *GASTROINTESTINAL SYSTEM , *JEJUNUM , *RADIATION EFFECTS , APOPTOSIS , BLOOD CELLS , BONE MARROW , DEPLETION , DOSAGE , HEMATOLOGY , HEMATOPOIETIC SYSTEM , IMPROVISED EXPLOSIVE DEVICES , IN VIVO ANALYSIS , PROTECTION , PROTEINS , RADIATION , RADIATION INJURIES , RECOVERY


Subject Categories : Medicine and Medical Research
      Radiobiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE