No abstract

The microscopic and ultrastructural characteristics of spontaneous pulmonary neoplasms in strain A (strA) mice are described. Fifty-one spontaneous lung tumors were identified in 34 out of 57, 11-23-month-old male strA/Hen mice. Grossly, all tumors appeared as yellow-white, discrete nodules ranging in size from 1.0-10 mm. Tumor types were randomly distributed throughout the lung; however, the right lung lobes were most frequently involved. Histologically, tumors were classified as adenoma (34/51) or carcinoma (17/51) as defined by standard histopathologic criteria. Adenomas were usually less than 4 mm in diameter and had solid (16/34), papillary (10/34), or mixed (8/34) histologic growth patterns. Carcinomas were usually greater than 4 mm in diameter and had papillary (13/17) or mixed (4/17) histologic growth patterns. Ultrastructurally, benign tumors consisted of solid or papillary areas of neoplastic type II-like cells. Cells comprising malignant tumors had varying ultrastructural characteristics ranging from well-differentiated alveolar cell types to undifferentiated cells having intracytoplasmic osmiophilic dense bodies, vacuoles, or few specialized organelles commonly observed in mature nonneoplastic pulmonary epithelial cells.

Male rats and male mice received a single 2-hr exposure to 0 (control), 10, or 30 ppm of methyl isocyanate and were sacrificed after 1, 3, 14, or 90 days to assess the ultrastructural changes in the nasal mucosa by transmission electron microscopy. One day after exposure to methyl isocyanate, there were widespread areas of necrosis and degeneration of the respiratory and olfactory epithelium of rats and mice in the 10 ppm and 30 ppm groups. Qualitatively the ultrastructural findings were similar for both exposure groups and species. Degeneration followed by rapid regeneration was observed for both respiratory and olfactory epithelia but was most striking for olfactory epithelium in the dorsal meatus. Three days after the exposure, the olfactory epithelium was two to three cell layers thick due to a loss of supporting cells, olfactory neurons, and basal cells. By 14 days after exposure, the olfactory epithelium was composed of a heterogeneous cell population three to five cell layers thick. At 90 days following exposure, the epithelium was of normal thickness (eight to ten cell layers), with normal architectural arrangement, and composed of well-differentiated cells that appeared similar to those of controls. There were several findings that suggested the epithelial cells of Bowman's glands were the progenitor for the regenerating supporting cells of the olfactory epithelium. This study demonstrated that the respiratory and olfactory epithelium is capable of complete structural regeneration after an acute destruction by methyl isocyanate.

Abstract. Intracytoplasmic hyaline globules were found frequently in chromaffin cells of the adrenal medulla from several species of laboratory animals that died from various causes. The globules stained intensely red with PAS, were weakly acid-fast, did not stain with oil-red 0 and showed bright yellow autofluorescence. Ultrastructurally , they were finely granular, round to oval, intensely osmiophilic and were surrounded by an intimately bound trilaminar membrane. The globules were interpreted as aggregated secretory granules that occur in degenerating cells.Intracytoplasmic hyaline globules in the adrenal medulla have been recognized in several animal species [ 5 , 91 including nonhuman primates [14]. They were first described in 1909 in people that died of infectious disease. These globules were interpreted as phagocytized erythrocytes [16]. Since then they have been found associated with various conditions including infectious disease, neoplasia and poisoning. Materials and MethodsThe adrenal glands from mice, rats, hamsters, guinea pigs, rabbits, dogs, opossums and Rhesus monkeys used in dibenzo-p-dioxin and chlorinated biphenyl toxicologic studies and from animals that died from spontaneous disease (mainly bacterial) were examined for intracytoplasmic hyaline globules in the chromaffin cells of the medulla. All tissues for light microscopy were collected soon after death and were fixed in 10 percent neutral buffered formalin. Sections were routinely stained with hematoxylin and eosin (HE). Special stains were periodic acid-Schiff (PAS), oil-red 0, Ziehl-Neelsen acid-fast and Millon's reaction for tyrosine [19].Parts of adrenal medulla for electron microscopy were removed from guinea pigs while the animals were anesthetized. Tissues were fixed in 2.5 percent glutaraldehyde and 2.0 percent paraformaldehyde in cacodylate buffer (pH 7.4) for 6 hours, washed with cacodylate buffer (pH 7.4), then put in 1 percent osmium tetroxide in cacodylate buffer (pH 7.4) for 2 hours, dehydrated in alcohol and propylene oxide, and embedded in epon 812. Thick sections (0.5 micrometers) for light microscopy were cut with an ultramicrotome and stained with toluidene blue. Thin sections, 400-600 x lo-' millimeters by interference color, were stained with uranyl acetate and Reynold's lead citrate [17]. 435

Abstract. Six primary interstitial cell tumors of the epididymis were identified from 46,752 male B6C3F, mice used in chronic toxicity and carcinogenicity studies. Five of the tumors occurred at the end of 2-year studies; none were attributed to treatment. None of the mice with epididymal tumors had a primary testicular tumor. Histologically, tumors were characterized by a nodular or diffuse proliferation of tumor cells in the epididymal interstitium. Most cells were polygonal with highly vacuolated cytoplasm (vacuolated cells) or eosinophilic cytoplasm (eosinophilic cells). Smaller hyperchromatic cells with scant basophilic cytoplasm (basophilic cells) and cells with yellow-brown pigment characteristic of lipofuscin (pigmented cells) were less common. In each tumor two or more cell types were present. Extension of these tumors through the capsule, invasion of the testis, or metastasis did not occur. By electron microscopy both eosinophilic and vacuolated cell types had a large round or oval nucleus with sparse heterochromatin, abundant mitochondria with tubulovesicular cristae, and frequent desmosome structures between cell membranes. Vacuolated cells contained numerous lipid droplets. Morphological features of the epididymal tumors are similar to those of the testicular interstitial (Leydig) cell tumor in mice and rats.