title: Insulin-like growth factor 1 mitigates hematopoietic toxicity after lethal total body irradiation.
abstract: OBJECTIVE
  To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation.
  
  
  METHODS
  BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system.
  
  
  RESULTS
  IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells.
  
  
  CONCLUSIONS
  IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Dunhua
authors.initials: D
authors.lastname: Zhou
authors.forename: Divino
authors.initials: D
authors.lastname: Deoliveira
authors.forename: Yubin
authors.initials: Y
authors.lastname: Kang
authors.forename: Seung S
authors.initials: SS
authors.lastname: Choi
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
authors.forename: Benny J
authors.initials: BJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006397:Hematinics / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D006397:Hematinics; D007334:Insulin-Like Growth Factor I