Cytoplasmic Inclusions in Spontaneous Hepatomas of CBA/H-T6T6 Mice. Histochemistry and Electron Microscopy2

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Abstract
Spontaneous hepatomas were found in 80% of adult male CBA/H-T6T6 mice, and a high proportion of these tumors had cytoplasmic Inclusion bodies (CIB). Three types of CIB were distinguished morphologically. By electron microscopy, the commonest (type 1) were membrane-bound bodies, arising within the rough endoplasmic reticulum of neoplastic cells. They were composed of a reticulated electron-dense component associated with a more diffuse granulofibrillary material. When mature, they were 1–20 μ in diameter; some filled the cells. By light microscopy, they were globular, hyaline, and eosinophilic. Most showed internal substructures (some eccentrically placed), were multiple, and stained differently from the general inclusion matrix. Type 2 CIB were less common, larger, and composed predominantly of fine granular matrix; however, they seemed to be related to type 1. Type 3 CIB were rare and resembled Mallory's hyalin. Types 1 and 2 consisted largely of protein and phospholipid without detectable nucleic acids or virus particles. Type 1 CIB were present only in the most highly differentiated neoplasms. Immunologic assay of sera from hepatoma-bearing animals revealed that 18% contained α-fetoprotein (AFP). AFP was more frequent in sera from animals with less differentiated tumors. No AFP was detected in the CIB. Type 1 and type 2 CIB represented material that had aggregated within the rough endoplasmic reticulum; however, the specific roles of increased production, decreased utilization, or defective transportation were not elucidated.