Carcinogenesis Advance Access originally published online on March 26, 2007
Carcinogenesis 2007 28(9):2041-2046; doi:10.1093/carcin/bgm071
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Swedish moist snuff accelerates gastric cancer development in Helicobacter pylori-infected wild-type and gastrin transgenic mice
1 Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NO-7006 Norway
2 Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 01451, USA
3 Department of Medical Microbiology, Lund University, Lund SE-22362, Sweden
4 Department of Clinical Microbiology, Malmö University Hospital, Malmö SE-20502, Sweden
5 Department of Oncology, St Olav's Hospital, Trondheim NO-7006, Norway
6 Division of Digestive and Liver Diseases, Columbia University Medical Center and Irving Cancer Research Center, NY 10032, USA
* To whom correspondence should be addressed. Tel: +47 725 73320; Fax: +47 725 76412; Email: duan.chen{at}ntnu.no
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 (GeneralTM; 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.
Abbreviations: CIS, carcinoma in situ; ECL, enterochromaffin-like; H.P., Helicobacter pylori; TSNA, tobacco-specific N-nitrosamines; WT, wild-type
Received January 24, 2007; revised March 16, 2007; accepted March 20, 2007.