Helicobacter pylori (Hp) infection and high-salt diet administration are both considered to be important factors in gastric carcinogenesis in man. To investigate the interaction of these two factors on gastric carcinogenesis, an experimental study of the carcinogenesis model was performed. Mongolian gerbils were treated with 20 ppm of N-methyl-N-nitrosourea (MNU) in their drinking water for alternate weeks for a total of 5 weeks' exposure (groups 1, 2, 3 and 4) or were maintained as controls (groups 5, 6, 7 and 8). At week 11, the animals were inoculated with Hp (groups 1, 2, 5 and 6) or the vehicle alone (groups 3, 4, 7 and 8), and after week 12, animals were fed a 10% high salt diet (groups 1, 3, 5 and 7) or the control diet (groups 2, 4, 6 and 8). At week 50, the incidence of adenocarcinomas in group 1 (32.1%, 6 well-differentiated, 2 poorly-differentiated adenocarcinomas, and one signet-ring cell carcinoma) was significantly higher than in groups 3 (0%) (P < < < <0.005) and 4 (0%) (P < < < <0.01). The incidence of adenocarcinomas in group 2 (11.8%, one well-differentiated adenocarcinoma, and one signet-ring cell carcinoma) was also higher than in groups 3 and 4. A high-salt diet enhanced the effects of Hp infection on gastric carcinogenesis, and these two factors acted synergistically to promote the development of stomach cancers. Moreover, Hp infection promoted gastric carcinomas more than the high-salt diet.

elicobacter pylori (Hp) is a major causative factor for gastric disorders and strong epidemiological evidence has been accumulated indicating a significant relationship with active chronic gastritis, peptic ulcers, atrophic gastritis, intestinal metaplasia, and malignant lymphoma or cancer development.

Summary To obtain information regarding the growth-inhibitory effect of 1,25-dihydroxyvitamin D3 and its non-calcaemic analogue 22-oxa-1,25-dihydroxyvitamin D3 on pancreatic cancer cell lines, differences in the effects of Gl-phase cell cycle-regulating factors were studied in vitamin D-responsive and non-responsive cell lines. Levels of expression of cyclins (D1, E and A), cyclin-dependent kinases (2 and 4) and cyclin-dependent kinase inhibitors (p21 and p27) were analysed by Western blotting after treatment with these compounds. In the responsive cells (BxPC-3, Hs 700T and SUP-1), our observations were: (1) marked up-regulation of p21 and p27 after 24 h treatment with 10-7 mol 1-' 1,25-dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3; and (2) marked down-regulation of cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors after 7 days' treatment. In non-responsive cells , no such changes were observed.In conclusion, vitamin D analogues up-regulate p21 and p27 as an early event, which in turn could block the G,/S transition and induce growth inhibition in responsive cells.

Intake of salt and salty food is known as a risk factor for gastric carcinogenesis. To examine the dose-dependence and the mechanisms underlying enhancing effects, Mongolian gerbils were treated with N-methyl-N-nitrosourea (MNU), Helicobacter pylori and food containing various concentrations of salt, and were sacrificed after 50 weeks. Among gerbils treated with MNU and H. pylori, the incidences of glandular stomach cancers were 15% in the normal diet group and 33%, 36% and 63% in the 2.5%, 5% and 10% NaCl diet groups, showing dose-dependent increase (p < 0.01). Intermittent intragastric injection of saturated NaCl solution, in contrast, did not promote gastric carcinogenesis. In gerbils infected with H. pylori, a high salt diet was associated with elevation of anti-H. pylori antibody titers, serum gastrin levels and inflammatory cell infiltration in a dose-dependent fashion. Ten percent NaCl diet upregulated the amount of surface mucous cell mucin (p < 0.05), suitable for H. pylori colonization, despite no increment of MUC5AC mRNA, while H. pylori infection itself had an opposing effect, stimulating transcription of MUC6 and increasing the amount of gland mucous cell mucin (GMCM). High salt diet, in turn, decreased the amount of GMCM, which acts against H. pylori infection. In conclusion, the present study demonstrated dose-dependent enhancing effects of salt in gastric chemical carcinogenesis in H. pylori-infected Mongolian gerbils associated with alteration of the mucous microenvironment. Reduction of salt intake could thus be one of the most important chemopreventive methods for human gastric carcinogenesis. ' 2006 Wiley-Liss, Inc.

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