Inhibition of radiation cataractogenesis by WR-77913.
The radioprotective drug S-3-amino-2-hydroxypropylphosphorothioic acid (WR-77913) has been tested as an inhibitor of radiation cataractogenesis. Animals treated with 15 Gy whole-head 137Cs gamma radiation developed mature cataracts 10-12 weeks after irradiation. Intraperitoneal pretreatment with 815 mg/kg WR-77913 30 min before irradiation delayed the development of cataracts; mature cataracts required 42 weeks for development. Doses as low as 350 mg/kg, substantially below the toxic range, resulted in graded but incomplete protection and a significant delay in the development of cataracts. Drug treatment combined with radiation doses of 12.5 or 10 Gy showed less pronounced protection. The optimum time of drug delivery was found to be between 30 min and 2 h before irradiation; protective action diminished if longer times were used or if the drug was given after irradiation. These results are discussed in relation to those obtained with other chemical radioprotective agents and in terms of possible mechanisms of the action of the drug.
Livesey
J C
JC
Department of Radiation Oncology, University of Washington, Seattle 98195.
Wiens
L W
LW
Von Seggern
D J
DJ
Barlow
W E
WE
Arnold
A M
AM
D004999:Amifostine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D002386:Cataract / Q000517:prevention & control*; D002588:Cesium Radioisotopes; D005720:Gamma Rays; D007908:Lens, Crystalline / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D008297:Male; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002588:Cesium Radioisotopes; D011837:Radiation-Protective Agents; C035284:WR 77913; D004999:Amifostine