title: Mouse model of diethylnitrosamine-induced gastric cancer.
abstract: 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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Binato
authors.forename: Marcelo
authors.initials: M
authors.lastname: Kruel Schmidt
authors.forename: Bernardo
authors.initials: B
authors.lastname: Silveira Volkweis
authors.forename: Guilherme
authors.initials: G
authors.lastname: Behrend Silva Ribeiro
authors.forename: Maria
authors.initials: M
authors.lastname: Isabel Edelweiss
authors.forename: Richard
authors.initials: R
authors.lastname: Ricachenevsky Gurski
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology; D004052:Diethylnitrosamine / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009602:Nitrosamines / Q000009:adverse effects / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; D004052:Diethylnitrosamine; D000431:Ethanol; C008655:N'-nitrosonornicotine