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Title: Protection from lethal irradiation by the combination of stem cell factor and tempol

Abstract

Cytokines that stimulate growth and differentiation of hematopoietic precursor cells have been used as protectors in vivo against ionizing radiation. Recently, we have shown that the nitroxide tempol is also an effective radiation protector in vivo. The purpose of the present study was to determine if the combination of tempol with stem cell factor (SCF, c-kit ligand) would provide enhanced radiation protection in C57 mice compared with the protection afforded by either agent alone. Mice were exposed to whole-body irradiation and assessed for survival at 30 days after irradiation. No control mice survived doses of more than 9 Gy. Treatment of mice before and after radiation with SCF alone (100 [mu]g/kg at -20 h, -4 h and +4 h) protected mice from radiation at doses of as high as 10 Gy (76% survival). Tempol (350 mg/kg) given 10 min prior to radiation was a radioprotector at 9 Gy (55% survival). The combination of SCF and tempol increased the survival of mice exposed to radiation doses up to 11 Gy (32% survival for the combination vs 4% for SCF alone and 0% for tempol alone; P < 0.001 for the combination vs either agent alone). Lower doses of SCF alone (1more » [mu]g/kg) or tempol alone (275 mg/kg) did not protect mice from radiation. However, the combination of these reduced doses of SCF and tempol protected mice from lethal irradiation at 10 Gy. Stem cell factor and tempol given either singly or together were well tolerated by the animals. These data show that SCF and tempol are radiation protectors and that their radioprotective effects are more than additive when the agents are given together. 16 refs., 2 figs., 2 tabs.« less

Authors:
; ; ;  [1];  [2]
  1. (National Cancer Institute, Bethesda, MD (United States))
  2. (AmGen Corp., Thousand Oaks, CA (United States))
Publication Date:
OSTI Identifier:
6479833
Resource Type:
Journal Article
Journal Name:
Radiation Research; (United States)
Additional Journal Information:
Journal Volume: 137:3; Journal ID: ISSN 0033-7587
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; LETHAL IRRADIATION; RADIATION PROTECTION; RADIOPROTECTIVE SUBSTANCES; SYNERGISM; BIOCHEMICAL REACTION KINETICS; MICE; STEM CELLS; WHOLE-BODY IRRADIATION; ANIMAL CELLS; ANIMALS; DRUGS; EXTERNAL IRRADIATION; IRRADIATION; KINETICS; MAMMALS; REACTION KINETICS; RODENTS; SOMATIC CELLS; VERTEBRATES; 560152* - Radiation Effects on Animals- Animals; 550200 - Biochemistry

Citation Formats

Liebmann, J., DeLuca, A.M., Mitchell, J.B., Steinberg, S.M., and Morstyn, G.. Protection from lethal irradiation by the combination of stem cell factor and tempol. United States: N. p., 1994. Web. doi:10.2307/3578716.
Liebmann, J., DeLuca, A.M., Mitchell, J.B., Steinberg, S.M., & Morstyn, G.. Protection from lethal irradiation by the combination of stem cell factor and tempol. United States. doi:10.2307/3578716.
Liebmann, J., DeLuca, A.M., Mitchell, J.B., Steinberg, S.M., and Morstyn, G.. Tue . "Protection from lethal irradiation by the combination of stem cell factor and tempol". United States. doi:10.2307/3578716.
@article{osti_6479833,
title = {Protection from lethal irradiation by the combination of stem cell factor and tempol},
author = {Liebmann, J. and DeLuca, A.M. and Mitchell, J.B. and Steinberg, S.M. and Morstyn, G.},
abstractNote = {Cytokines that stimulate growth and differentiation of hematopoietic precursor cells have been used as protectors in vivo against ionizing radiation. Recently, we have shown that the nitroxide tempol is also an effective radiation protector in vivo. The purpose of the present study was to determine if the combination of tempol with stem cell factor (SCF, c-kit ligand) would provide enhanced radiation protection in C57 mice compared with the protection afforded by either agent alone. Mice were exposed to whole-body irradiation and assessed for survival at 30 days after irradiation. No control mice survived doses of more than 9 Gy. Treatment of mice before and after radiation with SCF alone (100 [mu]g/kg at -20 h, -4 h and +4 h) protected mice from radiation at doses of as high as 10 Gy (76% survival). Tempol (350 mg/kg) given 10 min prior to radiation was a radioprotector at 9 Gy (55% survival). The combination of SCF and tempol increased the survival of mice exposed to radiation doses up to 11 Gy (32% survival for the combination vs 4% for SCF alone and 0% for tempol alone; P < 0.001 for the combination vs either agent alone). Lower doses of SCF alone (1 [mu]g/kg) or tempol alone (275 mg/kg) did not protect mice from radiation. However, the combination of these reduced doses of SCF and tempol protected mice from lethal irradiation at 10 Gy. Stem cell factor and tempol given either singly or together were well tolerated by the animals. These data show that SCF and tempol are radiation protectors and that their radioprotective effects are more than additive when the agents are given together. 16 refs., 2 figs., 2 tabs.},
doi = {10.2307/3578716},
journal = {Radiation Research; (United States)},
issn = {0033-7587},
number = ,
volume = 137:3,
place = {United States},
year = {1994},
month = {3}
}