This proposal bears on specific factors associated with the etiology of gastric cancer based on geographical pathology indicating that Northern Japan is a high-risk region for gastric cancer. Sanma hiraki, a type of fish often eaten in that region, was subjected to salting and pickling under laboratory conditions. This process yielded a mutagen for Salmonella typhimurium TA1535 responding to base pairing lesions without requiring metabolic activation. This behavior is consistent with this mutagen also being a direct-acting carcinogen. It was found that this agent was indeed a carcinogen for the glandular stomach in male Wistar strain rats. The chemical nature of this mutagen and carcinogen is not yet fully established. While a standard carcinogen for the glandular stomach typically is an alkylnitrosamide such as N-methyl-N'- nitro-nitrosoguanidine (MNNG), recent preliminary developments have suggested that the mutagen/carcinogen in nitrite-treated Sanma may be a diazonium hydroxide compound.
The aim of the current proposal is to fully validate this concept and actually identify the precursor promutagen. The present research is designed to isolate this chemical, establish its structure, and compare it with a synthetic sample. The chemical obtained by synthesis will be tested for carcinogenicity pursuant to the hypothesis that it is a carcinogen for the glandular stomach in rodent models.
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