Induction of Cancer of the Glandular Stomach in Rats by an Extract of Nitrite-Treated Fish23

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Abstract
Treatment of a homogenate of the mackerel fish Sanma hiraki with nitrite at pH 3 led to the development of direct-acting mutagenic activity for Salmonella typhimurium TA-1535. Repeated gastric incubation three times/week for 6 months of an extract containing this mutagenic activity into noninbred Wistar rats led to the induction of tumors in 8 of 12 rats 12–18 months later. Adenomas and adenocarcinomas were found in the glandular stomach, squamous cell carcinoma was observed in the forestomach, and adenocarcinoma was found in the small intestine and pancreas. Furthermore, precancerous lesions (including intestinal metaplasia and glandular hyperplasia of the glandular stomach as well as squamous cell hyperplasia) were noted in virtually all of the animals at risk. No tumors were seen in 8 control rats given the untreated fish extract alone; 1 rat had glandular hyperplasia and intestinal metaplasia. Thus a mutagenic extract of nitrite-treated fish was demonstrated to induce, in the rat glandular stomach, cancers identical to gastric cancer observed in man. Preventive measures, including reduction of the intake of pickled foods and the year-round dally availability of foods containing vitamin C, are discussed.