Abstract:
:Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inoculated dams intragestationally and/or pups postnatally, and evaluated offspring at 3, 6, or 12 months. Mice infected at or before 3 weeks of age, but not at 12 weeks, developed disease. Male mice were most affected, but expressed a bimodal pattern of susceptibility. Males exhibited lobular necrogranulomatous and interface (chronic active) hepatitis, while females usually developed intraportal (chronic persistent) hepatitis. Portal inflammation was slowly progressive, with tertiary lymphoid nodule development by 12 months. Hepatic bacterial load and preneoplastic lesions, including clear and tigroid cell foci of cellular alteration, were correlated with lobular hepatitis severity. No extrahepatic surrogate disease marker reliably predicted individual hepatitis grade. In conclusion, gender and bacterial exposure timing are key determinants of H. hepaticus disease outcomes. Intrahepatic inflammation is driven by local signals characterized by a vigorous but nonsterilizing immune response. Continued study of chronic hepatitis progression may reveal therapeutic targets to reduce the risk of hepatocellular carcinoma.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Rogers AB,Boutin SR,Whary MT,Sundina N,Ge Z,Cormier K,Fox JGdoi
10.1080/01926230490524247subject
Has Abstractpub_date
2004-11-01 00:00:00pages
668-77issue
6eissn
0192-6233issn
1533-1601pii
HL09FUNT3XC4CACYjournal_volume
32pub_type
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