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Related Experiment Videos

Sequential morphologic changes during methapyrilene-induced hepatocellular carcinogenesis in rats.

H M Reznik-Schüller, M Gregg

    Journal of the National Cancer Institute
    |November 1, 1983
    PubMed
    Summary

    Methapyrilene, an antihistamine, causes liver tumors in rats. These tumors, characterized by mitochondrial proliferation, exhibit features of oncocytomas, indicating a specific cellular transformation pathway.

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    Area of Science:

    • Hepatocellular Carcinogenesis
    • Toxicology
    • Mitochondrial Biology

    Background:

    • Hepatocellular tumors can arise from various etiological factors.
    • Understanding the cellular mechanisms of chemically induced liver cancer is crucial for risk assessment.

    Purpose of the Study:

    • To investigate the pathogenesis of hepatocellular tumors induced by the antihistamine methapyrilene in F344 rats.
    • To identify early cellular changes and track their progression to neoplastic lesions.

    Main Methods:

    • Light and electron microscopy were employed.
    • A serial sacrifice study design was utilized to observe changes over time.
    • Morphological criteria were used to classify lesions.

    Main Results:

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    • Eosinophilic foci of altered hepatocytes, marked by mitochondrial proliferation, were observed after 1 week of methapyrilene treatment.
    • These foci progressed to eosinophilic neoplastic nodules by 16 weeks.
    • Hepatocellular carcinomas developed by 26 weeks, retaining the mitochondrial proliferation characteristic of oncocytomas.

    Conclusions:

    • Methapyrilene induces hepatocellular tumors in rats through a process involving mitochondrial proliferation.
    • The resulting tumors exhibit morphological characteristics consistent with oncocytomas.
    • Mitochondrial proliferation serves as a key marker for methapyrilene-induced hepatocyte alteration and subsequent oncocytoma development.