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Biomedical subjects

J M Ward

Publications and source records attributed to J M Ward.

At least 343 records · Page 19Linked to original sources

Morphology and sex-dependent manifestation of nasal tumors in B6C3F1 mice after chronic inhalation of 1,2-dibromo-3-chloropropane.

Groups of 50 B6C3F1 mice of each sex were exposed to air containing of 1,2-dibromo-3-chloropropane at concentrations of 0.6 or 3.0 ppm for 6 hours per day, 5 days per week for 103 weeks. Untreated controls consisted of 50 mice of each sex. All surviving animals were killed at 104 weeks. Adenomas, squamous cell papillomas, adenocarcinomas, squamous cell carcinomas, carcinosarcomas, fibrosarcomas, and hemangiosarcomas of the nasal cavity occurred in male and female mice with dose related trends. Eighty-seven percent of the high dose female mice had nearly twice as many tumors as the high dose males (47%). Fourtynine percent of malignant neoplasms of the high dose female mice infiltrated the brain or metastasized to the lungs. Whereas two animals (4%) of the low dose female mice showed infiltrating carcinomas, no male mice exhibited this feature.

Animals↗

Morphology of hepatocellular neoplasms in B6C3F1 mice.

The morphology and behavior of hepatocellular neoplasms in control B6C3F1 mice were studied and classified according to cell size, tinctorial properties of the cytoplasm, pattern of growth, and other morphological features. The small tumors were composed primarily of basophilic hepatocytes which grew in a solid adenomatous pattern. Larger solid tumors had foci of prominent trabecular formations. All mice with metastatic hepatocellular neoplasms had large areas of prominent trabecular formations in the primary liver tumors. It appears that trabecular hepatocellular carcinomas develop from adenomatous neoplasms in the liver of B6C3F1 mice. The histogenesis and morphology of hepatocellular neoplasms in B6C3F1 mice is compared with those induced by carcinogens and differences are noted.

Adenoma↗

Lung tumors induced by chronic inhalation of 1,2-dibromo-3-chloropropane in B6C3F1 mice.

1,2-Dibromo-3-chloropropane (DBCP) was inhaled by B6C3F1 mice of each sex at concentrations of 0.6 or 3.0 ppm for 6 h/day, 5 days/week, for 103 weeks. Untreated controls consisted of 50 mice of each sex. All surviving animals were killed at 104 weeks. Survival in the high-dose groups of female mice was significantly shorter than that in the corresponding controls. Alveolar-bronchiolar adenomas or carcinomas occurred in both male and female mice with dose-related trends (P < 0.007) in males and (P < 0.002) in females. Papillary carcinomas in the lung occurred in low-dose female mice at an increased incidence compared with controls (P < 0.006). Many induced tumors were morphologically different than those in controls.

Adenocarcinoma, Bronchiolo-Alveolar↗

Unique toxic lesions induced by chemical carcinogens in rodents: indications of a short-term bioassy for carcinogenesis testing of environmental chemicals.

Many chemical carcinogens induce toxic nonneoplastic lesions relatively quickly (hours to weeks) in rodent tissues frequently the site of subsequent neoplasms, many months later. Although many of these toxic lesions are nonspecific, several unique lesions are induced almost entirely be carcinogens. Most commonly they are seen in rodent liver, kidney, thyroid and urinary bladder. If these lesions are induced in vivo by a chemical under safety testing, they may be predictive for future cancer development.

Animals↗

Morphology of nasal-cavity tumours in rats after chronic inhalation of 1,2-dibromo-3-chloropropane.

Groups of 50 F344 rats of each sex sere exposed to 0.6 or 3.0 pts/10(6) of 1,2-dibromo-3-chloropropane (DBCP) by inhalation for 6 h/day, 5 days/week for 103 weeks. Fifty rats of each sex inhaling filtered air were used as unexposed controls. All survivors were killed at 104 weeks. Up to 93% of the male and female rats developed neoplasms of the nasal cavity. Most of the tumours were adenomas, squamous-cell papillomas, squamous-cell carcinomas, and adenocarcinomas. In the low-dose group 78% of the tumours in males and 66% in females were benign, whereas in the high-dose groups 89% in males and 76% in females were malignant. Invasion through the cribriform plate into the cerebrum or metastasis to the regional lymph nodes was found in 73% of the carcinomas in males and 51% in females. Electron-microscopic examination suggested that the basal cells of the olfactory epithelium were the site of origin of the poorly differentiated adenocarcinomas.

Adenocarcinoma↗

Proliferative lesions of the spleen in male F344 rats fed diets containing P-chloroaniline.

Fifty male F344 rats were given diets containing 500 mg/kg P-chloroaniline. Controls received diets without the chemical. Eighteen of the dosed rats developed proliferative lesions of the spleen. Lesions included parenchymal fibrosis and fatty infiltration, well and poorly differentiated fibrosarcomas, osteosarcomas and hemangiosarcomas. All dosed rats had focal and diffuse fibrosis and papillary hyperplasia of the splenic capsule.

Aniline Compounds↗

Ganglioneuromas in the adrenal medulla of F344 rats.

Of 60,048 aging F344 rats, 28 had ganglioneuromas of the adrenal gland. The rats were between 58 and 122 weeks old; 25 of them between 93 and 122 weeks when the tumors were found. The neoplasms were composed of large or small typical ganglion cells with a large pale nucleus and a prominent, often eccentric, nucleolus. The ganglion cells usually were distributed throughout the medullary tumor and surrounded by various numbers of supporting cells, including Schwann's cell types, and capsular or satellite cells. Often there was no clear-cut border between ganglion cells and neoplastic pheochromocytes. Electron microscopy of re-embedded tissues showed neurosecretory granules and cytoplasmic areas with an extensive rough endoplasmic reticulum (Nissl substance) in the ganglion cells and axons. The Schwann's cells were surrounded by a basement membrane and formed long cytoplasmic extensions around the axons. Almost all ganglioneuromas were associated with neoplastic pheochromocytes which usually were located at the edge of the tumors.

Adrenal Gland Neoplasms↗

Morphological and histochemical characteristics of pigments in aging F344 rats.

Pigments found in spleen, lymph nodes, kidney, thyroid, adrenal, liver, ovary, central nervous system, heart and connective tissues of aging F344 rats were studied morphologically and histochemically. The morphology of the pigment accumulations depended on the tissue affected. Pigments resembling lipofuscin were found in most of these tissues. The ultrastructural appearance of siderosomes in splenic macrophages suggested that erythrocyte degradation was responsible for pigment production. Adrenal ultrastructure showed that lipofuscin-like material may have originated from degradation of lipid droplets of epithelial cells.

Adrenal Glands↗

Histopathologic differences between liver tumors in untreated (C57BL/6 X C3H)F1 (B6C3F1) mice and Nitrofen-fed mice.

A comparison was made of the histologic characteristics of naturally occurring and Nitrofen-induced liver tumors in (C57BL/6 X C3H)F1 (B6C3F1) mice. Whereas induced tumors generally consisted of solid sheets or nodules of frequently enlarged eosinophilic hepatocytes containing enlarged and/or hyperchromatic nuclei, the spontaneous neoplasms consisted predominantly of small basophilic cells containing oval or round nuclei and frequently arranged in trabeculae 1--2 cells wide. Within the livers of Nitrofen-treated animals, foci of hepatocytes resembling those within the tumor masses were also observed in the nonneoplastic areas. Metastases were not present in the lungs of any controls, whereas small emboli or large masses of neoplastic hepatocytes were present in incidences up to 29% in treated mice with tumors. This bioassay provides evidence that, in some cases, liver tumors in treated mice are morphologically different from those in controls and suggests that Nitrofen induces unique liver tumors rather than acts as a promoter of spontaneous neoplasms.

Animals↗

Histogenesis and morphology of naturally occurring prostatic carcinoma in the ACI/segHapBR rat.

The prostates of 201 male virgin or breeder ACI (ACI/segHapBR) rats, 24 to 40 months of age were reviewed histologically, and the genesis of prostatic carcinoma was studied. At 24 months of age, 35 to 45 per cent of the rats had the earliest lesions, intraalveolar atypical hyperplasias. These lesions progressed to intraalveolar cribriform carcinomas which spread along alveoli and ducts. As the tumors enlarged, they became nodular and invaded the capsule or adjacent tissues. By 33 months, 95 to 100 per cent of the rats had intraalveolar prostatic atypical hyperplasias, and 35 to 40 per cent had invasive carcinomas. There was no difference between the incidence of these tumors in virgin or breeder rats. The ACI rat is unique model for studying the etiology and pathogenesis of naturally occurring prostatic cancer.

Adenocarcinoma↗

Neoplastic and nonneoplastic lesions in aging (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice.

Neoplastic and nonneoplastic lesions in untreated (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice used as controls in carcinogenesis tests were tabulated and evaluated. The most common neoplasms in 2,543 male mice were hepatocellular adenomas and carcinomas. In 2,522 female mice, common tumors were lymphomas, leukemias, pulmonary adenomas and carcinomas, hepatocellular adenomas and carcinomas, and pituitary adenomas. The risk of developing most neoplasms increased with the age of the mouse. Hepatocellular carcinomas metastasized in 12% of the animals with these tumors. Other than lymphomas and leukemias, few other tumors metastasized. Nonneoplastic lesions included cystic hyperplasia of the uterus, nephritis, ovarian and uterine cysts, inflammatory lesions of the lung, mineralization in the brain, and focal hyperplasias in several tissues. The focal hyperplasias in lung and pituitary, adrenal, and thyroid glands were suggestive of the early stages of neoplasia. Comparative aspects of lesions in aging mice and their interpretation in carcinogenesis tests are discussed.

Age Factors↗

Neoplasms and pigmentation of thyroid glands in F344 rats exposed to 2,4-diaminoanisole sulfate, a hair dye component.

2,4-Diaminoanisole sulfate was fed at dietary levels of 0.12% (low dose) or 0.5% (high dose) to groups of 50 male and 50 female inbred F344 rats for 78 weeks. By 107 weeks after the initial exposure, 58% of the male rats and 42% of the female rats administered the high dose had thyroid neoplasms, whereas only 7--8% of the controls developed them. Follicular cell carcinomas were the primary type of neoplasm induced. None of the controls had these tumors. The carcinomas, which were papillary, cystic, or solid, were highly invasive but did not metastasize. A brown pigment was present as granules primarily in thyroid follicular cells in all exposed rats. The amount of pigment as determined by an image-analyzing computer revealed that the cross-sectional area occupied by the pigment granules and the optical density of the granules were dose related.

Adenocarcinoma↗