Journal Article

Swedish moist snuff accelerates gastric cancer development in <i>Helicobacter pylori</i>-infected wild-type and gastrin transgenic mice

Björn Stenström, Chun-Mei Zhao, Arlin B. Rogers, Hans-Olof Nilsson, Erik Sturegård, Steinar Lundgren, James G. Fox, Timothy C. Wang, Torkel M. Wadström and Duan Chen

in Carcinogenesis

Volume 28, issue 9, pages 2041-2046
Published in print September 2007 | ISSN: 0143-3334
Published online March 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm071
Swedish moist snuff accelerates gastric cancer development in Helicobacter pylori-infected wild-type and gastrin transgenic mice

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The Swedish variant of moist oral smokeless tobacco (snus) is popular in Sweden and Norway, banned from sale within the European Union and is currently being introduced in USA. The aim of the present study was to determine if snus is carcinogenic to the stomach, particularly in Helicobacter pylori (H.P.)-infected hosts at increased risk for gastric cancer development. Snus (General™; Swedish Match, Sweden) was mixed with powdered standard mouse chow at a concentration of 5–9% (wt/wt) and given to wild-type (WT, FVB) and gastrin transgenic (INS-GAS, FVB) mice for 6 months with or without H.P. (strain 67:21, CagA+, VacA+) infection. At necropsy, pathological evaluation of stomachs from uninfected snus-treated WT mice showed mild morphological changes, whereas 50% snus-treated INS-GAS mice developed carcinoma in situ (CIS), compared with 25% not exposed to snus. When snus was given to H.P.-infected mice, 9 of 17 WT mice developed CIS with intramucosal invasion, and the remaining 8 of 17 WT mice developed high-grade dysplasia (score >1.5) that was associated with increased gastritis, epithelial defects, oxyntic atrophy, hyperplasia and intestinal metaplasia. Twelve of 12 H.P.-infected INS-GAS mice developed CIS with intramucosal invasion and submucosal herniation. We suggest that snus is a potential gastric carcinogen in mice. The development of CIS was associated with increased rates of the epithelial cell proliferation and apoptosis, common features of gastric carcinogenesis.

Journal Article.  4133 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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