In vivo screening of radioprotectors. Annual summary report, March 1982-March 1983
Technical Report
·
OSTI ID:5276109
Twenty-eight agents were evaluated for drug toxicity, and 30 agents were tested for radioprotectant activity. A total of 35 new agents were evaluated in all. Eleven of the compounds tested protected irradiated mice and produced 70% survival or greater in mice exposed to a radiation dose lethal to nonprotected animals. Only one agent, a relative nontoxic phosphorothioate (WR 250397), protected 100% of treated mice at a dose of 1200 mg/kg. The radioprotectant standard WR 2721, for comparison, provides 100% protection when administered at doses between 200 and 600 mg/kg. Six of eight agents were entered into detailed evaluation for radioprotectant activity. Detailed testing includes primary protectant screening and determination of: degree of protection, time of maximum protection, duration of protection, and effectiveness of oral drug formulation. Radiation-dose-modification studies conducted with intraperitoneally administered WR 2721 and WR 168643 indicated a Dose Modification Factor (DMF) of 2.2 and 1.1 for WR 2721 and WR 168643, respectively. WR 168643 and WR 3689 given orally produced DMF values of 1.3 and 1.5, respectively. Duration of protection with orally administered WR 2721 exceeded 90 minutes. Radiation protection with orally or intraperitoneally administered WR 168643 lasted approximately 30 minutes. Protection with WR 3689 appeared to last less than one hour following ip injection but was greater than two hours following oral injection. Preliminary toxicity and radioprotection screening studies were completed for three other known radioprotectant compounds WR 1065, WR 77913, and WR 176542.
- Research Organization:
- Little (Arthur D.), Inc., Cambridge, MA (USA)
- OSTI ID:
- 5276109
- Report Number(s):
- AD-A-168500/7/XAB
- Country of Publication:
- United States
- Language:
- English
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