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Inhibition of ß-Propiolactone-induced Neoplasia of the Forestomach and Large Bowel by 4-Mercaptobenzene Sulfonate in Mice and Rats¹

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

Studies have been initiated to find compounds that can trap direct-acting carcinogens within the lumen of the gastrointestinal tract and thus prevent these carcinogens from attacking tissues of the host. Sodium 4-mercaptobenzene sulfonate (4-MBSNa) is a potent nucleophile and was found to react rapidly in vitro with the direct-acting carcinogen ß-propiolactone (BPL). In further investigations 4-MBSNa was shown to inhibit mutagenesis resulting from exposure of Salmonella typhimurium strain TA-100 to BPL and a second direct-acting carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine. Subsequent experiments were performed to determine if 4-MBSNa would inhibit BPL-induced carcinogenesis in vivo. In the first of these, 4-MBSNa was administered by p.o. intubation to female A/J mice 5 min before p.o. administration of BPL. Under these conditions inhibition of carcinogenesis of the forestomach occurred. In a second experiment, 4-MBSNa was given by rectal intubation 5 min before BPL also administered intrarectally. Administration of BPL intrarectally produced adenomatous polyps of the large intestine. The occurrence of these neoplasms was inhibited by the prior administration of 4-MBSNa. The data presented show that 4-MBSNa has the capacity to trap direct-acting carcinogens and to inhibit the occurrence of BPL-induced neoplasia.

¹ Supported by USPHS Grant CA-43285 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at University of Minnesota, Laboratory Medicine and Pathology, P. O. Box 609, Mayo Building, 420 Delaware Street SE, Minneapolis, MN 55455-0315.

Received 11/17/87. Revised 2/ 8/88. Accepted 2/16/88.