Radioprotective effects of various cytokines in peripheral blood mononuclear cells and C3H mice.
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.
Kim
Ju Young
JY
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Oh
Suk Joong
SJ
Park
Hyun Ki
HK
Yoon
Jin Sun
JS
Kim
Eun Shil
ES
Kim
Eun Sil
ES
Kim
Chong Soon
CS
Lee
Young Yiul
YY
Kim
Byoung Kook
BK
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
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