Development of high-grade lymphoma in Helicobacter pylori-infected C57BL/6 mice.

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. Mice with H. pylori infection develop severe gastritis and atrophic changes in their stomachs after 6 months. We followed H. pylori-infected animals for 13 months to find out whether dysplasia, carcinoma or lymphoma developed. Six-week-old C57BL/6 mice were infected with the CagA-positive and VacA-positive H. pylori mouse-passaged strain 119/95, fed a low antioxidant diet, and kept in microisolated cages. Histopathological changes were examined after 13 months' infection. All H. pylori-inoculated mice (n = 5) developed a gastric squamous papilloma with nagging of the lamina muscularis after 13 months. Three out of five animals developed high-grade B-cell lymphoma derived from a MALT lymphoma at the squamous-corpus border with manifestations also in the liver, spleen and kidney. There was a suspicion of local gastric lymphoma in the two remaining mice but with no significant changes in the liver, spleen or kidney. The normal control mice showed no pathological changes in any of these organs. It is concluded that this mouse model with infection by the CagA-positive, vac-toxin-producing H. pylori strain 119/95 is suitable for use in the study of lymphoma development and also development of squamous cell papilloma with proliferative features.