Helicobacter pylori but not high salt induces gastric intraepithelial neoplasia in B6129 mice

被引:114
作者
Rogers, AB
Taylor, NS
Whary, MT
Stefanich, ED
Wang, TC
Fox, JG
机构
[1] MIT, Div Comparat Med, Cambridge, MA 02139 USA
[2] Columbia Univ, Coll Phys & Surg, Div Digest & Liver Dis, New York, NY USA
关键词
D O I
10.1158/0008-5472.CAN-05-1846
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Helicobacter pylori is responsible for most human stomach cancers. Gastric cancer also is overrepresented in populations consuming high-salt diets. Attempts to test the hypothesis that high salt promotes H. pylori carcinogenesis have been hindered by the lack of a wild-type mouse model. Based on pilot observations of unexpectedly early gastric adenocarcinoma in C57BL/6 x 129S6/SvEv (B6129) mice infected with Helicobacter felis, we conducted a study to characterize H. pylori infection in these mice and to determine whether high salt promotes tumorigenesis. Male and female mice were gavaged with H. pylori Sydney strain-1 or vehicle only and divided into four groups based on infection status and maintenance on a basal (0.25%) or high (7.5%) salt diet. In uninfected mice, the high-salt diet enhanced proliferation and marginally increased parietal cell mucous metaplasia with oxyntic atrophy. Lesions in H. pylori infected mice without regard to diet or gender were of equivalent severity and characterized by progressive gastritis, oxyntic atrophy, hyperplasia, intestinal metaplasia, and dysplasia. Infected mice on the high-salt diet exhibited a shift in antimicrobial Immoral immunity from a Th1 to a Th2 pattern, accompanied by significantly higher colonization and a qualitative increase in infiltrating eosinophils. No mice developed anti-parietal cell antibodies suggestive of autoimmune gastritis. At 15 months of age infected mice in both dietary cohorts exhibited high-grade dysplasia consistent with gastric intraepithelial neoplasia. In summary, we report for the first time H. pylori-indticed gastric intraepithelial neoplasia in a wild-type mouse model and show no additive effect of high-salt ingestion on tumor progression. (Cancer Res 2005; 65(23): 10709-15).
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页码:10709 / 10715
页数:7
相关论文
共 34 条
[1]  
[Anonymous], 1994, IARC Monogr Eval Carcinog Risks Hum, V61, P1
[2]   Helicobacter pylori infection and high dietary salt independently induce atrophic gastritis and intestinal metaplasia in commercially available outbred mongolian gerbils [J].
Bergin, IL ;
Sheppard, BJ ;
Fox, JG .
DIGESTIVE DISEASES AND SCIENCES, 2003, 48 (03) :475-485
[3]   Pathology of mouse models of intestinal cancer: Consensus report and recommendations [J].
Boivin, GP ;
Washington, K ;
Yang, K ;
Ward, JM ;
Pretlow, TP ;
Russell, R ;
Besselsen, DG ;
Godfrey, VL ;
Doetschman, T ;
Dove, WF ;
Pitot, HC ;
Halberg, RB ;
Itzkowitz, SH ;
Groden, J ;
Coffey, RJ .
GASTROENTEROLOGY, 2003, 124 (03) :762-777
[4]  
CORREA P, 1992, CANCER RES, V52, P6735
[5]  
Correa Pelayo, 2004, IARC Sci Publ, P301
[6]   The future of gastric cancer prevention [J].
Correa P. ;
Piazuelo M.B. ;
Camargo M.C. .
Gastric Cancer, 2004, 7 (1) :9-16
[7]  
Crowe SE, 2005, CURR OPIN GASTROEN, V21, P32
[8]   GASTRIC CANCER AND DIET - A PILOT STUDY ON DIETARY HABITS IN 2 DISTRICTS DIFFERING MARKEDLY IN RESPECT OF MORTALITY FROM GASTRIC CANCER [J].
DUNGAL, N ;
SIGURJONSSON, J .
BRITISH JOURNAL OF CANCER, 1967, 21 (02) :270-+
[9]   Host and microbial constituents influence Helicobacter pylori-induced cancer in a murine model of hypergastrinemia [J].
Fox, JG ;
Wang, TC ;
Rogers, AB ;
Poutahidis, T ;
Ge, ZM ;
Taylor, N ;
Dangler, CA ;
Israel, DA ;
Krishna, U ;
Gaus, K ;
Peek, RM .
GASTROENTEROLOGY, 2003, 124 (07) :1879-1890
[10]  
Fox JG, 2003, CANCER RES, V63, P942