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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 inHelicobacter 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 withoutH.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 carcinomain situ(CIS), compared with 25% not exposed to snus. When snus was given toH.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 &gt;1.5) that was associated with increased gastritis, epithelial defects, oxyntic atrophy, hyperplasia and intestinal metaplasia. Twelve of 12H.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.

carcinogenesis

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