Helicobacter pylori infection enhances glandular stomach carcinogenesis in Mongolian gerbils treated with chemical carcinogens

Abstract

Helicobacter pylori (Hp) is thought to be a stomach carcinogen from epidemiological findings. To determine the effects of infection with the bacteria on experimental carcinogenesis, a study of the glandular stomach of Mongolian gerbils (MGs) was performed. Male MGs were treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by inoculation with Hp or infected with Hp followed by N-methyl-N'-nitro-N-nitrosoguanidine administration. Animals were killed at week 50, and their excised stomachs underwent microbiological and histopathological examinations. In addition, a serological investigation was performed. The incidences of adenocarcinomas were significantly higher in animals treated with 60 or 300 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 10 weeks followed by Hp inoculation or Hp followed by 20 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 30 weeks than in the respective controls. Moreover, tumour-bearing animals had higher titres of anti-Hp antibodies than tumour-free animals. Of interest was the finding that a dose of 100 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine given to infected gerbils eradicated the Hp in about half the animals, with a concomitant reduction in the promoting effect. No tumours were found in animals infected with Hp without N-methyl-N'-nitro-N-nitrosoguanidine or non-treated gerbils. Hp infection enhances glandular stomach carcinogenesis in MGs treated with N-methyl-N'-nitro-N-nitrosoguanidine. Animals with high titres of anti-Hp antibodies are at greatest risk of developing neoplasms.

Emergence of spasmolytic polypeptide-expressing metaplasia in Mongolian gerbils infected with Helicobacter pylori

“…23,25,30 Previous studies have documented that Hp-infected Mongolian gerbils develop intestinal metaplasia and can further progress to gastric cancer. 30 We have reported that SPEM associates human early gastric cancer more frequently than intestinal metaplasia and SPEM is also a gastric precancerous lesion.…”

“…[22][23][24][25][26] In addition, Hp infection promotes tumor development in the gerbil model. [23][24][25]27 While previous investigations have noted the presence of some intestinal metaplasia in gerbils, the role of SPEM in the genesis of gastric mucosal changes in gerbils is uncertain. In this study, we have examined the time course for metaplastic changes in fundic glands and the relationships between SPEM and goblet cell intestinal metaplasia in Hp-infected Mongolian gerbils.…”

Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis

“…However, the overall, H. pylori antibody titers were lower, and in particular, they were significantly lower as compared with that in the low-intake group among the non-elderly (o65 years old) subjects. In general, higher H. pylori antibody titers correlate with more active H. pylorirelated CAG, as shown in clinical and animal studies (Eaton and Krakowka, 1992;Shimizu et al, 1999;Loffeld et al, 2000;Nozaki et al, 2002). In particular, in H. pylori-infected Mongolian gerbils, higher antibody titers are associated not only with more active gastritis, but also with a higher incidence of gastric cancer (Shimizu et al, 1999).…”

“…In general, higher H. pylori antibody titers correlate with more active H. pylorirelated CAG, as shown in clinical and animal studies (Eaton and Krakowka, 1992;Shimizu et al, 1999;Loffeld et al, 2000;Nozaki et al, 2002). In particular, in H. pylori-infected Mongolian gerbils, higher antibody titers are associated not only with more active gastritis, but also with a higher incidence of gastric cancer (Shimizu et al, 1999). In light of these previous findings, our results suggest that although JA intake does not eradicate established H. pylori infection from the gastric mucosa, it may, by virtue of a direct bactericidal action on H. pylori and anti-inflammatory effects, decrease the severity of gastritis.…”

Helicobacter pylori infection and Gastric Cancer.

“…Metaplasia may then progress to gastric cancer, especially to tumors that are intestinal (52). Recently, Shimizu et al conducted a carcinogenesis experiment by infecting Mongolian gerbils with H. pylori and reported that progression to gastric cancer was chiefly seen in animals that showed a high H. pylori antibody titer (59). To consider the association between H. pylori infection and the onset of diffuse type of gastric cancer, the process from infection with H. pylori through gastric mucosal atrophy, intestinal metaplasia, and developmentof cancer must be ex- As has been discussed, there is little doubt that persistent infection with H. pylori is closely related to the development of gastric cancer.…”