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A female congenic rat produced by repeated backcrossing of Nihon rats, a model for hereditary renal cell carcinoma, to Brown Norway rats was necropsied at 24 months of age. At necropsy, a white mass about 1 centimeter in size was observed in the thoracic cavity, and the mass partly adhered to the esophagus and the diaphragm. Histologically, the mass was clearly circumscribed by connective tissue, and consisted of neoplastic cuboidal epithelial cells that showed cystic tubular proliferation. Some islands of well-differentiated hepatocytes and some vessels were observed in the mass. Immunohistochemically, the tumor cells were strongly positive for cytokeratin and partly positive for vimentin but were negative for mesothelin and Von Willebrand Factor. The positive rate for Ki-67 was 2.4%. Based on these histological and immunohistochemical evidences, we diagnosed this tumor as a cystic cholangioma that might have arisen from the ectopic hepatic tissue in the thoracic cavity.

In the present study, we investigated the histological, immunohistochemical and ultrastructural characteristics of cytoplasmic blood plasma inclusions that spontaneously occurred in a rat liver. Histologically, a number of cytoplasmic inclusions were observed in the liver of an 8-week-old female SD rat. These inclusions were strongly positive for PAS staining and resistant to diastase digestion. Immunohistochemical analyses revealed that these inclusions were positive for albumin and IgG; however, most of them were negative for LAMP-1 and LAMP-2. Ultrastructurally, the inclusions were surrounded by limiting membranes and composed of moderately electron dense, homogenous materials. These characteristics described here represent valuable information for pathological examination in toxicity studies.

An immunohistochemical staining method for prohibitin, a 30-kDa protein located in the inner membrane of mitochondria, is used for detection of mitochondria on formalin-fixed paraffin-embedded sections. Methapyrilene hydrochloride (MP), which is known to increase mitochondria in periportal hepatocytes, was administered once by oral gavage to male rats at a dose of 100 mg/kg. Hypertrophy with eosinophilic granules was noted in the periportal hepatocytes treated with MP. Immunohistochemical staining with prohibitin antibody demonstrated a positive reaction to eosinophilic granules. Electron microscopy showed an increased number of mitochondria in the periportal hepatocytes treated with MP compared to the control. Although electron microscopy is a useful tool to detect ultrastructural changes, an immunohistochemical examination with anti-prohibitin antibody is a simple and easy method for detecting cytoplasmic mitochondria quantitatively.

Promotion effects of sodium L-ascorbate (Na-AsA) on two-stage urinary bladder carcinogenesis were examined in male NCI-Black-Reiter (NBR) rats, which lack a2u-globulin-synthesizing ability, and F344 rats for comparison of the action. The animals were initiated with exposure to 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) via the drinking water for 4 weeks, and then treated with a basal diet containing a 5% supplement of Na-AsA or no added chemical for 32 weeks. The urinary pH and Na ion concentration in both strains of rats treated with BBN followed by Na-AsA (BBN→Na-AsA) were significantly higher than those in the matched controls (BBN alone). Microscopically, significantly increased incidences of papillary or nodular hyperplasia, papillomas, and transitional cell carcinomas were observed in F344 rats treated with BBN →Na-AsA, whereas the incidences of these lesions in NBR rats were comparable in the BBN→Na-AsA and BBN alone cases. These data indicate NBR rats to be resistant to Na-AsA-induced promotion of two-stage urinary bladder carcinogenesis. Since the elevation of urinary parameters generally associated with tumor promotion by Na-AsA was a feature with both strains, another factor such as a2u-globulin, may also be active for enhancement of lesion development.