Protective effects of S-2-(3-aminopropylamino)ethylphosphorothioic acid against radiation damage of normal tissues and a fibrosarcoma in mice.
S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR-2721) was investigated for its protective effect against radiation-produced damage of jejunum, testis, lung, hair follicles, and a fibrosarcoma of C3Hf/Kam mice. Most of these tissues were radioprotected, and the degree of radioprotection depended on the dose of WR-2721 and the time interval between administration of WR-2721 and radiation treatment. WR-2721 increased resistance of jejunal epithelial cells and spermatogenic cells to single doses of gamma-rays by factors of 1.64 and 1.54, respectively. Protection against hair loss was less pronounced; the dose-modifying factor here was 1.24. The radiation-induced acute damage of the lung expressed by the increased formation of tumor nodules in the lung was not decreased by treatment of animals with WR-2721 before radiation. In contrast, WR-2721 augmented the radiation-induced enhancement of metastasis formation in the lung. WR-2721 protected fibrosarcoma micrometastases in the lung against therapeutic effect of radiation by a factor of 1.238. In contrast, this compound had no effect on the therapy of an 8-mm fibrosarcoma growing in the legs of mice.
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology / Q000532:radiotherapy*; D005720:Gamma Rays; D007583:Jejunum / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000209:etiology / Q000556:secondary; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000473:pathology / Q000532:radiotherapy; D013737:Testis / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects
D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; D004999:Amifostine