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

Journal Article · Tue Mar 01 04:00:00 EST 1994 · Radiation Research; (United States)

DOI:https://doi.org/10.2307/3578716· OSTI ID:6479833

Liebmann, J; DeLuca, A M; Mitchell, J B; Steinberg, S M ^[1]; Morstyn, G ^[2]

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1. National Cancer Institute, Bethesda, MD (United States)
2. AmGen Corp., Thousand Oaks, CA (United States)

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.

• OSTI ID: 6479833
• Journal Information: Radiation Research; (United States), Journal Name: Radiation Research; (United States) Vol. 137:3; ISSN 0033-7587; ISSN RAREAE
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560152* -- Radiation Effects on Animals-- Animals
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
DRUGS
EXTERNAL IRRADIATION
IRRADIATION
KINETICS
LETHAL IRRADIATION
MAMMALS
MICE
RADIATION PROTECTION
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RODENTS
SOMATIC CELLS
STEM CELLS
SYNERGISM
VERTEBRATES
WHOLE-BODY IRRADIATION