Mallory body-like abnormalities in carcinomas induced by cultured transformed rat liver cells

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Abstract
Hepatoma cells isolated from rats after administration of a carcinogen, diethylnitrosamine, and propagated in culture, contained a genetically stable cytoskeletal abnormality resembling Mallory bodies. These juxtanuclear aggregates of intermediate-sized filaments were maintained in carcinomas produced in nude mice after inoculation of uncloned mass cultures and a cloned subculture. Paraffin and frozen sections of these tumors revealed acentric nuclei and a glassy hyalin-type cytoplasmic lesion which stained pink with hematoxylin-eosin and blue with Mallory’s aniline blue stain. The cells in culture and in the tumor sections were strongly positive for γ-glutamyl transpeptidase. Cryostat sections examined by indirect immunofluorescence microscopy with antisera to purified bovine hoof prekeratin, desmosome-associated tonofilaments from bovine muzzle, and murine vimentin, as well as transmission electron microscopy revealed the presence of juxtanuclear aggregates of intermediate-sized filaments. All characteristics previously reported for the tissue culture cell line were stably maintained in the tumor tissue. These results suggest that the Mallory body-containing cells frequently observed in man in alcoholic hepatitis and other degenerative liver diseases could, under appropriate environmental “promoting” conditions, be precursor cells in focal hepatocellular carcinoma formation.