Protection by S-2-(3-aminopropylamino)ethylphosphorothioic acid against radiation-induced leg contractures in mice

S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR-2721) was shown to provide marked protection against development of radiation-induced leg contractures in C3Hf/Kam mice whose legs were exposed to single doses of gamma-radiation. The radiation doses ranged from 3300 to 6200 rads delivered to the right hind thighs from two parallelly opposed 137Cs sources. WR-2721 was given i.p. 30 min before irradiation. The severity of radiation-induced leg contractures in untreated and WR-2721-treated mice was followed for 342 days after irradiation. The degree of leg contractures in both control and WR-2721-treated mice increased up to 100 days after radiation, when the change stabilized, remaining more or less at the same level to the end of the observation period. During this entire period, the severity of contractures was less in WR-2721-treated mice. The dose-modifying factor for the level of 5 mm reduction in leg extension was 1.5 at 182 days after irradiation. Since WR-2721 did not prevent the radiocurability of 8-mm fibrosarcomas growing in the same legs, these data imply that WR-2721 has a high potential for increasing therapeutic gain when combined with irradiation in the treatment of tumors of an appreciable size.