Radioprotection of tumor and normal tissues by thiophosphate compounds.

Abstract

The efficacy of the radioprotective thiophosphate compounds WR638 (sodium hydrogen S-[2 aminoethyl] phosphorothioate) and WR2721 (S-2-[3-amino-propylamino] ethyl phosphorothioate) was determined for a wide range of normal tissue and tumor endpoints. Dose-modifying factors (D.M.F.) were obtained for mouse skin, small intestine, bone marrow, esophagus, lung, and kidney. D.M.F. values were also obtained for the P-388 leukemia, the EMT-6 mouse mammary carcinoma assayed in vitro, and the EMT-6 mammary carcinoma assaysed for cure. The D.M.F. values obtained for normal tissue ranged from 1.2 for lung to 3 for bone marrow CFU's. The D.M.F. values for tumor ranged from 1.3 for cure of the EMT-6 carcinoma to 2.2 for mean survival time in the P-388 leukemia. There appears to be a decreasing dose-modifying factor as a function of increasing dose in both tumor and normal tissue systems. The degree of protection afforded tumors appears to relate to their vascularization and their anoxic cell component. Although the D.M.F. obtained for cure of the solid EMT-6 carcinoma would appear to be lower than for normal tissues with single doses, the data presently available do not allow one to predict that such a beneficial effect would occur with the multiple small doses used clinically.