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Infect. Immun., 05 1996, 1548-1558, Vol 64, No. 5
JG Fox, X Li, L Yan, RJ Cahill, R Hurley, R Lewis and JC Murphy
Helicobacter hepaticus causes hepatitis in selected strains of mice and in
A/JCr mice is linked to liver cancer. To analyze whether H. hepaticus
persists in specified ecological niches, to determine whether biomarkers of
infection exist, and to analyze the influence of H. hepaticus on hepatocyte
proliferation, a longitudinal study of H. hepaticus-infected A/JCr mice was
undertaken. A/JCr mice were serially euthanatized from 3 through 18 months
and surveyed by enzyme-linked immunosorbent assay; bacterial culture of
liver, colon, and cecum; histology; electron microscopy; hepatocyte
proliferation indices determined by using 5-bromo-2'-deoxyuridine; and
measurement of the liver enzyme alanine aminotransferase. In infected
animals throughout the 18-month study, H. hepaticus was consistently
isolated from the lower bowel but only sporadically from the liver. By
electron microscopy, H. hepaticus was noted infrequently and only in bile
canaliculi. Infected mice, particularly males, showed chronic inflammation;
oval cell, Kupffer cell, and Ito cell hyperplasia; hepatocytomegaly; and
bile duct proliferation. The inflammatory and necrotizing lesion was
progressive and involved the hepatic parenchyma, portal triads, and
intralobular venules. Hepatic adenomas were noted only in male mice,
whereas 5-bromo-2'-deoxyuridine proliferation indices were markedly
increased in both sexes, but especially in males, compared to control A/J
mice. Infected mice also developed sustained anti-H. hepaticus serum
immunoglobulin G antibody responses and elevated alanine aminotransferase
levels. H. hepaticus, which persists in the lower bowels and livers of
A/JCr mice, is associated with a chronic proliferative hepatitis, and
hepatomas in selected male mice indicate that this novel bacterium may
cause an increased risk of hepatic cancer induction in susceptible strains
of mice. This murine model should prove useful in dissecting the molecular
events operable in the development of neoplasms induced by bacteria
belonging to this expanding genera of pathogenic Helicobacter species.
Copyright © 1996, American Society for Microbiology
Chronic proliferative hepatitis in A/JCr mice associated with persistent Helicobacter hepaticus infection: a model of helicobacter- induced carcinogenesis
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, USA.
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