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Selenium pretreatment enhances the radioprotective effect and reduces the lethal toxicity of WR-2721

Technical Report ·
OSTI ID:6019883
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Although WR-2721, S-2-(3-aminopropylamino) ethylphosphorothioic acid, is an effective radioprotector, its use is limited by its toxicity. Combining WR-2721 with other agents might decrease its toxicity and/or increase its effectiveness. The effect of selenium (Se) pretreatment on the acute toxicity and radioprotective effect of WR-2721 was studied in male CD2F1 mice. Injection of 1.6 mg/kg Se 24 hr before WR-2721 (800-1200 mg/kg, IP) decreased the lethality of WR-2721 significantly. Lower doses of Se were also effective, but simultaneous administration was not effective. Se injection alone (1.6 mg/kg) 24 hr before cobalt-60 irradiation increased the survival significantly. A synergistic effect on post-rirradiation survival was observed when Se was injected 24 hr before WR-2721. Alkaline phosphatase activity in bone marrow cells and serum was significantly depressed after treatment with 1.6 mg/kg Se, suggesting that a retardation of conversion of WR-2721 to its active free sulfhydryl form through the action of alkaline phosphatase might be partly responsible for the effects of Se. Other possible mechanisms related to the antioxidant properties of Se are under investigation.

Research Organization:
Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)
OSTI ID:
6019883
Report Number(s):
AD-A-183268/2/XAB; AFRRI-SR-87-22
Country of Publication:
United States
Language:
English

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Related Subjects

560100* -- Biomedical Sciences
Applied Studies-- Radiation Effects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
ANTIOXIDANTS
BIOLOGICAL EFFECTS
BODY
BONE MARROW
DRUGS
ELEMENTS
ENZYMES
ESTERASES
HEMATOPOIETIC SYSTEM
HYDROLASES
MAMMALS
MICE
ORGANS
PHOSPHATASES
RADIATION PROTECTION
RADIOPROTECTIVE SUBSTANCES
RODENTS
SELENIUM
SEMIMETALS
SYNERGISM
TISSUES
TOXICITY
VERTEBRATES