Experimental model of upper intestinal adenocarcinoma induced by N-methyl-N′-nitro-N-nitrosoguanidine in C57BL/6 mice

The purpose of this study was to develop a model of gastrointestinal carcinogenesis using C57BL/6 mice. Treatment regimens consisted of one control group and 2 groups which received N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in drinking water: 50 μg/ml × 52 weeks and 100 μg/ml × 27 weeks. In addition, 2 protocols using adjuvant agents intended to increase tumor formation were used: MNNG (100 μg/ml) × 27 weeks + 0.2% taurocholic acid added to the diet from weeks 13–52, and MNNG (50 μg/ml) × 33 weeks + caerulein (10 μg/kg) subcutaneously 3 times/week from weeks 21–52. High-grade dysplasia was observed in the duodenum of 1/13 mice treated with MNNG (50 μg/ml). The combination of the latter and caerulein did not augment tumorigenesis. Mice treated with MNNG (100 μg/ml) frequently developed neoplasia in the duodenum and upper jejunum. Foci of low-grade and high-grade dysplasia alone were found in 3/12 (25%) mice; and intramucosal and invasive adenocarcinoma were found in 7/12 (58.3%) mice. The addition of taurocholic acid significantly increased the number and histological stages of the tumors (adenocarcinoma occurred in 100%, P = 0.03) and decreased the time for tumor formation.