Pre-treatment with rapamycin protects hematopoiesis against radiation injury

Background: protection of hematopoietic system has become a primary goal inthe development of novel medical countermeasures against ionization radiationand radiotherapy. this study was to explore the role of rapamycin in normal tissuesagainst radiation. materials and methods: mice were pretreated with rapamycinby i.p. every other day for five times before 5 gy or 8.5 gy γ-ray whole bodyirradiation. blood cell counts, he staining of bone marrow and liver, bone marrowtransplantation, cfu of spleen were used to measure the damage of hematopoiesisand extramedullary hemopoietic organs. regular karyotype analysis and expressionof γ-h2ax (by flow cytometry and western blot) were used to measure dnadamage. rad 50 and dna lig 4 expression by western blot were to see the dnarepair ability. results: the decrease of red blood cells and platelet induced byradiation were alleviated by pretreatment with rapamycin (d 7,15, p<0.01),and the long-term restoration of white blood cells, lymphocytes and bonemarrow were enhanced in rapamycin pretreatment group (d 30,40,70,p<0.05). the transplantation experiment also indicates that the long-termreconstitution in lethally irradiated recipient mice was improved in rapamycingroup (p<0.05). the hepatocellular injury by radiation was also reduced andthe colony formation numbers of spleen a=er irradiation was improved inrapamycin group (p<0.05). karyotype analysis indicates that rapamycinprotected bone marrow cells from chromosome mutation. furthermore,expression of dna repair proteins rad 50 and dna lig 4 was enhanced anddna damage marker γ-h2ax was reduced in mice exposed to radiation byrapamycin pretreatment. conclusion: rapamycin pretreatment mitigateshematopoietic system from radiation injury in both bone marrow andextramedullary hematopoietic organs by improving genomic stability and increasingsurvival of hematopoietic stem and progenitor cells (hspcs).