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Induction of Glandular Stomach Cancers in C3H Mice Treated with N-Methyl-N-nitrosourea in the Drinking Water



Establishment of an animal model of stomach carcinogenesis in mice was attempted using N-methyl-N-nitrosourea (MNU) in the drinking water. One hundred and forty-eight male 6-week-old C3H mice were given MNU in their drinking water at a concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group 3) or 0 ppm (group 4) for 30 weeks. At the end of this time, dose-related induction of adenomatous hyperplasias was found. From weeks 31 to 54 adenocarcinomas developed in a dose-dependent manner in groups 1, 2 and 3. In total, 6 well differentiated and 5 poorly differentiated adenocarcinomas as well as 6 signet ring cell carcinomas arose in 15 stomach cancer-bearing animals in group 1, 4 well differentiated and 2 poorly differentiated adenocarcinomas with one signet ring cell carcinoma in 5 mice of group 2 and one well differentiated adenocarcinoma in group 3. In the forestomach, only one squamous cell carcinoma was found at week 54 in group 1 along with a single well differentiated adenocarcinoma in the duodenum. Thus, MNU in the drinking water selectively induced neoplastic lesions in the glandular stomach epithelium of mice.