HYPERTROPHIC GASTROPATHY IN HELICOBACTER-FELIS - INFECTED WILD-TYPE C57BL 6 MICE AND P53 HEMIZYGOTIC TRANSGENIC MICE/

Background & Aims: Helicobacter pylori infection causes gastritis and peptic ulcers and is linked epidemiologically to gastric cancer, To an alyze host genetic factors and the influence of Helicobacter on cell p roliferation, we used an inbred and p53 hemizygous mouse model of Heli cobacter felis-induced gastritis, Methods: H. felis was inoculated by gastric intubation into SPF C57BL/6 wild-type and p53 hemizygous mice that were followed up for 1 year and compared with uninfected controls of the same genotype using histology, proliferating cell nuclear anti gen (PCNA) staining, and 5-bromo-2'-deoxyuridine (BrdU) analysis, Resu lts: Infected animals developed sustained anti-H, felis serum immunogl obulin G antibody responses. Six months after infection, both wild-typ e and p53 hemizygous mice showed active chronic inflammation and marke d mucosal hyperplasia compared with uninfected controls, One year afte r infection with H. felis, the wildtype and p53 hemizygous mice showed severe adenomatous and cystic hyperplasia of the surface foveolar epi thelium, BrdU uptake and PCNA staining were markedly increased in both sets of infected mice compared with controls, Infected p53 hemizygous mice had a higher proliferative index than the infected wild-type mic e, Conclusions: H. felis can induce a hypertrophic gastropathy in the C57BL/6 genotype; loss of one p53 allele, although insufficient to ini tiate carcinogenesis at 1 year, enhances the proliferative index, whic h may lead to an increased risk of cancer induction.