Comparison of radioprotective effects of WR-2721 and WR-3689

WR-2721, S-2-(3-aminopropylamino)ethyl phosphorothioic acid, is a very effective radioprotectant, but it is desirable to find a drug that is less toxic and more effective when administered orally. Evidence exists that the less toxic WR-3689, S-2-(3-methylaminopropylamino) ethyl phosphorothioic acid, may be more effective when given orally. In the present study, radioprotective effects of these two compounds administered at equitoxic doses were compared in male CD2F1 mice. The LD/sub 50/ of cobalt-60 (100 rad/min) more than doubled in mice treated i.p. before irradiation with either WR-2721 (400 mg/kg) or WR-3689 (450 mg/kg). Treatment p.o. with WR-2721 (700 mg/kg) 1 or 2 hr before irradiation provided better protection than WR-3689 (1000 mg/kg) with survival increased from 850 to 1300 rad. Effects of dietary administration of drugs on postirradiated survival and on tissue levels of enzymes that protect against oxidative damage were also studied. The effect of drugs on radiation-induced suppression of delayed-type hypersensitivity was determined. Oral treatment with WR-2721 was slightly more effective than treatment with WR-3689 in protecting cell-mediated immunity. These studies do not indicate that WR-3689 is a more effective oral radioprotectant than WR-2721, but further studies using different drug doses and treatment schedules are necessary