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Related Experiment Videos

Hepatocarcinogenesis in the mouse. Combined morphologic-stereologic studies.

H Koen, T D Pugh, S Goldfarb

    The American Journal of Pathology
    |July 1, 1983
    PubMed
    Summary

    Early hepatocellular carcinoma development in mice involves microscopic lesions that invade blood vessels before forming larger tumors. These findings suggest classifying early lesions as microcarcinomas, aiding cancer research.

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    Area of Science:

    • Hepatocarcinogenesis research
    • Mouse models of cancer
    • Liver pathology

    Background:

    • Trabecular hepatocellular carcinomas develop over time following exposure to carcinogens.
    • Early microscopic changes precede the formation of fully developed tumors.

    Purpose of the Study:

    • To investigate the histogenesis of trabecular hepatocellular carcinomas in diethylnitrosamine-induced mouse liver cancer.
    • To identify early cellular changes and their correlation with tumor progression and invasion.

    Main Methods:

    • Male B6C3 F1 mice were injected with diethylnitrosamine (DENA) at 15 days old.
    • Liver tissues were examined at 10, 20, and 28 weeks post-injection.
    • Serial sectioning was used to identify and measure microscopic foci and nodules, noting venous invasion and ductule proliferation.

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    Main Results:

    • Basophilic hepatic foci, characterized by increased nuclear-to-cytoplasmic ratio, were observed as early as 10 weeks post-DENA injection.
    • Venous invasion in foci correlated with increasing size, preceding the development of thickened hepatic plates seen in later-stage tumors.
    • Proliferation of bile ductules within foci increased with lesion size, suggesting encroachment on surrounding bile ducts.

    Conclusions:

    • Early, small, invasive lesions (microcarcinomas) in the liver are predisposed to developing into trabecular hepatocellular carcinomas.
    • The size of the focus is a critical factor in the development of venous invasion.
    • This DENA-induced mouse model is suitable for studying tumor growth kinetics due to the localized nature of the lesions.