Mouse model of diethylnitrosamine-induced gastric cancer.
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.
Binato
Marcelo
M
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.
Kruel Schmidt
Marcelo
M
Silveira Volkweis
Bernardo
B
Behrend Silva Ribeiro
Guilherme
G
Isabel Edelweiss
Maria
M
Ricachenevsky Gurski
Richard
R
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
D002273:Carcinogens; D009602:Nitrosamines; D004052:Diethylnitrosamine; D000431:Ethanol; C008655:N'-nitrosonornicotine