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Section of Gastrointestinal Oncology and Digestive Diseases, Department of Medical Oncology [M. J. W., C. W.], and Division of Veterinary Medicine and Surgery [L. C. S., K. G.], The University of Texas, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030, and Ludwig Institute for Cancer Research [V. W. S. E.], Toronto, Ontario M4Y 1M4, Canada
Diallyl sulfide (DAS) is a principal thioether of garalic (Allium sativum) accounting, in part, for the flavor and fragrance of this herb. Previous studies have shown that DAS is a potent inhibitor of experimentally induced colon cancer in mice. Metabolic studies of other garlic-derived substances suggested that DAS could prevent tumorigenicity of other hepatic activated carcinogens. The present study was designed to determine whether DAS could inhibit the DNA-damaging and tumorigenic effects of N-Nitrosomethylbenzylamine in rat esophagus. A dose of 200 mg/kg of DAS given p.o. 3 h prior to N-nitrosomethylbenzylamine administration was found to inhibit the carcinogen-induced nuclear toxicity by 64% to 56% at the two doses (3 and 5 mg/kg) of NMBA tested. These results suggested that the compound was potentially anticarcinogenic. In the carcinogenicity experiment it was found that DAS totally inhibited tumor formation in rats treated with a carcinogenic dose of NMBA (100% inhibition of papilloma and squamous cell carcinoma incidence, P < 0.0001). Additionally DAS was found to substantially reduce hepatic microsomal metabolism of the carcinogen. These data demonstrate that DAS is unique in its anticarcinogenic activity. It strongly suppresses the tumorigenic effects of potent, metabolically activated monoalkylating carcinogens in the gastrointestinal tract.
1 Supported in part by a grant from the Milheim Foundation for Cancer Research; Development Funds, The University of Texas System Cancer Center; and by National Cancer Institute Cancer Center Support (Grant CA-16672), Centralized Histopathology Laboratory.
2 To whom requests for reprints should be addressed, at Section of Gastrointestinal Oncology and Digestive Diseases, Box 78, University of Texas-M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
Received 6/ 3/88. Revised 8/16/88. Accepted 8/18/88.
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