Abstract
We have investigated the radioprotective efficacy and the cellular metabolism of several phosphorylated derivatives of cysteamine, with particular reference to comparison of normal and malignant cells. Two compounds have been studied in detail: S-2-(3-aminopropylamino) ethyl phosphorothioic acid (WR2721) and sodium hydrogen S-(2-aminoethyl) phosphorothioate (WR638). Both agents protect euoxic marrow-colony forming units (CFUs) in vivo better than cysteamine when the cells are treated with both drug and x-radiation prior to transplantation. Under these conditions, the DMF for WR2721 is 3.0 and for WR638, 2.3. Hypoxic CFUs are protected only slightly, the net result being to lower the oxygen enhancement ratio (OER) to 1.1 with WR2721 and 1.3 with WR638. Both compounds also protect euoxic tumor cells (Ehrlich carcinoma and P388 leukemia growing as ascites tumors) with a DMF of approximately 2; anoxic tumors are not protected. Biochemical studies disclose that the thiophosphates enter cells by passive diffusi...
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