We purified male rat urinary alpha(2u)-globulin, prepared the antibody in rabbits, and improved an immunohistochemical detection method using this antibody for male rat-specific alpha(2u)-globulin accumulation appearing as hyaline droplets in the kidneys. Our prepared antibody reacted specifically with alpha(2u)-globulin in both immunohistochemical and Western blotting analyses, furthermore, and the graded immuno-reactivities on the slide were well associated with computational image analyzing results. Using this method, we retrospectively analyzed the renal sections from the toxicity studies of 12 nephrotoxic chemicals, which had already been conducted under the Japanese Existing Chemicals Survey Program. We demonstrated that the hyaline droplets induced by treatment with 10 chemicals (1,4-dibromobenzene, dicyclopentadiene, 3,4-dimethylaniline, 1,4-dicyanobenzene, tetrahydrothiophene-1,1-dioxide, 1,3-dicyanobenzene, acenaphthene, 3,4-dichloro-1-butene, 3a,4,7,7a-tetrahydro-1H-indene and 3,5,5-trimethylhexan-1-ol) were directly associated with alpha(2u)-globulin accumulation. This immunohistochemical method is convenient for applying, even retrospectively, paraffin sections from general toxicity studies and could be useful for qualifying male rat-specific hyaline droplets consisting of alpha(2u)-globulin and renal risk in humans.

A tumor was observed in the left mandible of a 3-year-old male Shih-Tzu dog. Histopathology revealed neoplastic alveolar proliferation of round cells, sarcomatoid proliferation of round to spindle-shaped cells and an existing parotid gland tissue around the tumor. A cancellous bone framework was also seen throughout the tumor. The tumor cells in the sarcomatoid area were positive and weakly positive for vimentin and cytokeratin, respectively, demonstrating their myoepithelial character. We diagnosed this tumor as a malignant mixed tumor of the salivary glands, because of the location of the tumor, its invasiveness into the surrounding tissue and the identification of both epithelial and myoepithelial tumor cells.

Abstract:In a study to collect background data using c-Ha-ras transgenic mice (rasH2 mice), epithelial proliferative lesions were observed in the nasal cavities of the animals with or without administration of a single intraperitoneal dose of N-methyl-N-nitrosourea (MNU). These proliferative lesions occurred most frequently in the ventral meatus of the incisive papilla (nasal cavity in the specimen). Most of the proliferative lesions were a polypoid or papillary form consisting mainly of an epithelium resembling a squamous epithelium. In addition, administration of MNU tended to increase the incidence of proliferative lesions. Therefore, in carcinogenicity studies using rasH2 mice, we may come across epithelial proliferative lesions in the nasal cavity. (J Toxicol Pathol 2008; 21: 193-197)