title: Radioprotective effects of various cytokines in peripheral blood mononuclear cells and C3H mice.
abstract: The purpose of this study was to investigate the radioprotective effect of HGFs (GM-CSF, IL-3 and SCF) in irradiated human peripheral blood mononuclear cells (PBMCs) in vitro, and the survival effect of lethally irradiated C3H mice in vivo. The irradiation of human PBMCs using a (137)Cs irradiator showed a dose-dependent inhibition of cell growth up to a dose of 5 Gy. This cell growth inhibition induced apoptosis, which was associated with the down-regulation of Bcl-2, up-regulation of Bax, depolarization of mitochondrial transmembrane potential (Delta psi m), and caspase-3 and -9 activation. Following gamma-irradiation at 2 Gy, IL-3 (10 ng/ml) alone or combined with SCF (50 ng/ml) reduced the apoptotic portion of human PBMCs by 15 and 20% of the cell population, respectively, showing no activation of caspase-3 compared to the control group. To examine the in vivo effect of gamma-irradiation and cytokines, we investigated the survival rate and recovery of peripheral blood cells in C3H mice. C3H mice subjected to total body irradiation (TBI) at a dose of 7 Gy (lethal dose 83% at 30 days) showed time-dependent decreases in RBC, WBC and platelet counts, with the nadir occurring at 12 to 15 days. However, treatment with recombinant murine (rm) SCF (2 microg/day s.c.), rmIL-3 (2 microg/day s.c.), or rmG-CSF (2.5 microg/day s.c.) 24 h before and after irradiation did not promote hematologic recovery or survival in the lethally irradiated C3H mice. These findings indicate that the combined treatment of IL-3 and SCF prevents the apoptosis induced in PBMCs by gamma-irradiation in vitro, but it does not afford any in vivo radioprotective effect in lethally irradiated C3H mice.
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Suk Joong
authors.initials: SJ
authors.lastname: Oh
authors.forename: Hyun Ki
authors.initials: HK
authors.lastname: Park
authors.forename: Jin Sun
authors.initials: JS
authors.lastname: Yoon
authors.forename: Eun Shil
authors.initials: ES
authors.lastname: Kim
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Kim
authors.forename: Chong Soon
authors.initials: CS
authors.lastname: Kim
authors.forename: Young Yiul
authors.initials: YY
authors.lastname: Lee
authors.forename: Byoung Kook
authors.initials: BK
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000494:pharmacology*; D007377:Interleukin-3 / Q000097:blood / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000097:blood / Q000494:pharmacology*; D015996:Survival Rate; D014916:Whole-Body Irradiation; D051028:bcl-2-Associated X Protein
chemical_list: C494827:Bax protein, mouse; D007377:Interleukin-3; D019253:Proto-Oncogene Proteins c-bcl-2; D011837:Radiation-Protective Agents; D019089:Stem Cell Factor; D051028:bcl-2-Associated X Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases