Effects of eradication of Helicobacter pylori on gastric carcinogenesis in experimental models

Helicobacter pylori infection enhances glandular stomach carcinogenesis in Mongolian gerbils (MGs) treated with N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea. A high-salt diet has been revealed to synergistically enhance development of stomach cancer with H. pylori infection; the latter exerts stronger promoting effects than the former. Eradication of H. pylori with antibiotics diminishes their enhancing effects. The earlier the eradication of H. pylori is undergone, the more effective is the prevention of gastric carcinogenesis in MGs. To explore whether the role of H. pylori infection is a cause of stomach carcinogenesis (initiator) or just a supporting actor (promoter), we established an experimental model of long-term (2 years) H. pylori infection and eradication in MGs without chemical carcinogens. Long-term H. pylori infection stimulated development of highly proliferative and dilated glands containing a large amount of mucin, called heterotopic proliferative glands (HPGs), resembling mucinous adenocarcinomas. However, no gastric carcinomas were found in MGs after 2 years of H. pylori infection in our system. After eradication of the bacteria, HPGs were obviously reduced, and gastric lesions were mostly alleviated. These findings showed that H. pylori infection is related to severe gastritis and that HPGs are frequently induced reversible lesions rather than being malignant in character. Helicobacter pylori infection thus appears to have a strong promotional influence but not to initiate gastric carcinogenesis.