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Studies on Latent Derivatives of Aminoethanethiols as Potentially Selective Cytoprotectants

II. In Vivo Distribution of Cysteamine Liberated in Rat Tissues¹

Collaborative Research, Inc., Waltham, Massachusetts

Preliminary evaluation of latent cytoprotectants as potentially useful chemotherapeutic compounds that would protect normal tissue against damaging effects of radiation or alkylating agents has involved examination of 11 candidate compounds for their capacity to release cysteamine after these compounds were injected into Sprague-Dawley rats. Cysteamine-S-phosphate and cysteamine-S-sulfate released substantial concentrations of cysteamine in a number of tissues, the former by an enzymatic process, the latter by a nonenzymatic mechanism. Only small concentrations of cysteamine were detected following the injection of N-acetylcysteamine, S-acetylcysteamine, N,S-diacetyl-cysteamine or 2-methylthiazoline. Little or no cysteamine was observed when the following compounds were tested: O-methyl-cysteamine-S-phosphate, and the N-(2-mercaptoethyl)carbamoyl derivatives of the amino acids phenylalanine, methionine, alanine, and ß-alanine. These data are correlated with available radiation protection information.

¹ Supported by Research Contract PH43-62-170, Cancer Chemotherapy National Service Center, National Cancer Institute, NIH, Bethesda, Md.

² Department of Biochemistry, Tufts University School of Medicine, Boston, Mass.

Received 5/ 3/66. Accepted 8/19/66.

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