Mouse Model of Diethylnitrosamine-Induced Gastric Cancer

Binato, Marcelo; Kruel Schmidt, Marcelo; Silveira Volkweis, Bernardo; Behrend Silva Ribeiro, Guilherme; Isabel Edelweiss, Maria; Ricachenevsky Gurski, Richard

doi:10.1016/j.jss.2007.12.748

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Volume 148, Issue 2 , Pages 152-157, August 2008

Mouse Model of Diethylnitrosamine-Induced Gastric Cancer

Marcelo Binato, M.D.
- Department of General Surgery, Division of Digestive Surgery, Hospital de Clínicas de Porto Alegre, Medical School, Federal University of Rio Grande do Sul, Rio Grande do Sul, Brazil
Marcelo Kruel Schmidt, M.D.
- Department of General Surgery, Division of Digestive Surgery, Hospital de Clínicas de Porto Alegre, Medical School, Federal University of Rio Grande do Sul, Rio Grande do Sul, Brazil
Bernardo Silveira Volkweis, M.D.
- Department of General Surgery, Division of Digestive Surgery, Hospital de Clínicas de Porto Alegre, Medical School, Federal University of Rio Grande do Sul, Rio Grande do Sul, Brazil
Guilherme Behrend Silva Ribeiro, M.D.
- Department of General Surgery, Division of Digestive Surgery, Hospital de Clínicas de Porto Alegre, Medical School, Federal University of Rio Grande do Sul, Rio Grande do Sul, Brazil
Maria Isabel Edelweiss, M.D., Ph.D.
- Department of Pathology, Hospital de Clínicas de Porto Alegre, Medical School, Federal University of Rio Grande do Sul, Rio Grande do Sul, Brazil
Richard Ricachenevsky Gurski, M.D., Ph.D.
- Department of General Surgery, Division of Digestive Surgery, Hospital de Clínicas de Porto Alegre, Medical School, Federal University of Rio Grande do Sul, Rio Grande do Sul, Brazil
- To whom correspondence and reprint requests should be addressed at 188 Luiz Manoel Gonzaga st. # 301, Porto Alegre, Rio Grande do Sul 90470-280, Brazil.

Received 17 April 2007 published online 06 May 2008.

Background

Nitrosamines are associated with the potential to induce cancer in the digestive tract. Ethanol has also been shown to enhance the effects of nitrosamine-induced carcinogenesis. The aim of this study was to investigate a murine model of the prevalence and types of epithelial lesions induced in the stomach by diethylnitrosamine (DEN), and to evaluate the influence of ethanol and N′-nitrosonornicotine (NNN) as promoters of gastric carcinogenesis.

Materials and methods

Two hundred eight (n = 208) mice were distributed into five groups and administered either water (G1), DEN+water (G2), DEN+NNN (G3), DEN+Ethanol (G4), or DEN+NNN+Ethanol (G5) for a period of 180 days. Mice were sacrificed; their stomachs were sectioned and stained with hematoxylin/eosin. Stomachs were analyzed for normal histology; foveolar hyperplasia; gastritis; ulcer; adenoma; metaplasia; dysplasia; squamous-cell cancer (SCC); and adenocarcinoma (ACA).

Results

One hundred eighty-four (N = 184) specimens were studied. No statistically significant differences were observed between the average DEN consumption of groups (P > 0.05). Unlike G1, in all four groups exposed to carcinogens, gastric SCC and ACA were induced (P < 0.001). SCC was identified in 91 (49.5%) and ACA in 77 (41.8%) of all mice (including controls). In 47 mice (25.5%), we identified two histological types of carcinoma that occurred simultaneously. The prevalence of ACA in G5 was higher when compared with the other exposed groups (P < 0.001).

Conclusions

We created an optimal murine model for investigation of the development of gastric carcinogenesis, as there was a high rate of development of tumors, but low mortality and morbidity. The coadministration of DEN, ethanol, and NNN induced carcinogenesis to the largest extent compared with the other combinations.

Key Words: diethylnitrosamine, ethanol, nitrosamines, carcinogenesis, gastric adenocarcinoma, gastric squamous-cell tumor, gastric cancer