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Inhibition of ß-Propiolactone-induced Mutagenesis and Neoplasia by Sodium Thiosulfate¹

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455

Studies have been initiated to find compounds that can trap directacting carcinogens within the stomach. Sodium thiosulfate (STS) is a potent nucleophile and in initial experiments was found to inhibit mutagenesis resulting from exposure of Salmonella typhimurium strain TA100 to the direct-acting carcinogens ß-propiolactone and styrene oxide. In in vitro experiments STS was shown to maintain its nucleophilicity in the acid pH range. It reacted with ß-propiolactone as rapidly at pH 2 as at pH 7.4. Thus STS has the prerequisite attributes to inhibit the carcinogenic effects of electrophiles in the stomach. Experiments were performed in which STS was administered by p.o. intubation to female A/J mice 5 min before p.o. administration of ß-propiolactone. Under these conditions, inhibition of formation of the forestomach tumors occurred. The data obtained suggest that use of nucleophiles to protect against direct-acting carcinogens is a potential strategy for chemoprevention.

¹ Supported by USPHS Grant CA-43285 from the National Cancer Institute and Grant SIG-5A from the American Cancer Society.

² To whom requests for reprints should be addressed.

Received 2/13/87. Revised 5/ 1/87. Accepted 5/26/87.