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Protection by S-2-(3-Aminopropylamino)ethylphosphorothioic Acid against Radiation-induced Leg Contractures in Mice¹

Department of Experimental Radiotherapy, The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Houston, Texas 77030

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 -radiation. The radiation doses ranged from 3300 to 6200 rads delivered to the right hind things 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.

¹ This investigation was supported in part by NIH Grants CA-06294 and Ca-16672 and the author's institutional funds. (Account 175439). Animals used in this study were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care and in accordance with current regulations and standards of the United States Department of Health and Human Services, NIH.

² To whom requests for reprints should be addressed, at Department of Experimental Radiotherapy, The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, 6723 Bertner Avenue, Houston, Texas 77030.

Received 6/21/82. Accepted 1/11/83.