Manik Chandra

Spontaneous neoplasms in aged sprague-dawley rats

Incidence of neoplastic lesions in untreated Sprague-Dawley rats (1340 males and 1329 females) used as controls in 17 carcinogenicity studies are tabulated and evaluated. In male rats, the most common neoplasms were benign pheochromocytomas and keratoacanthomas (4.0% in each case) followed by pancreatic islet cell adenomas (3.7%), thyroid parafollicular cell adenomas (3.6%), fibromas and squamous cell papillomas of the skin and hepatocellular adenomas (2.0% in each), malignant lymphoma lymphocytic (1.9%), histiocytic sarcomas (1.4%), and adrenal cortical adenomas (1.2%). In female rats, the most common neoplasms were of mammary gland origin (31.3%: fibroadenoma 19.0%, adenocarcinomas 8.8%, and adenomas 3.5%) followed by thyroid parafollicular cell adenomas (2.9%), uterine endometrial stromal polyps (2.6%), adrenal cortical adenomas (1.9%), malignant lymphoma lymphocytic (1.6%), fibromas in the skin (1.3%), and pancreatic islet cell adenoma (1.1%). Metastases were observed from pheochromocytomas, hepatocellular carcinomas, nephroblastomas, renal pelvis transitional cell carcinoma, interstitial cell tumor and seminoma of the testes, Zymbals gland adenocarcinomas, and mammary adenocarcinomas.

The Morphology, Immunohistochemistry, and Incidence of Hematopoietic Neoplasms in Mice and Rats:

Hematopoietic neoplasms in the rodent may be classified into lymphoid or nonlymphoid neoplasms. Lymphoid neoplasms include the following morphologic types: follicular center cell, lymphoblast (lymphocytic), immunoblast, plasma cell, and large granular lymphocyte (LGL). Nonlymphoid hematopoietic neoplasms include histiocytic sarcoma, granulocytic leukemia, erythroid leukemia, and mast cell tumors. Most types of hematopoietic neoplasms, exclusive of LGL lymphoma (leukemia), are more common in mice than in rats. Specific strains of mice have a hematopoietic tumor incidence of more than 50% in aged animals. Some strains of rats (i.e., Fischer-344) may have an incidence of over 50% of LGL lymphoma in aged animals. The tumor type and incidence are characteristic for each rat or mouse strain. Hematopoietic neoplasms have been better characterized immunomorphologically in mice than in rats. The specific cell type and tissue of origin for hematopoietic neoplasms may be important for safety evaluation of chemicals. Specific chemicals may induce specific types of these tumors, which may be the same or different from the spontaneous types. Lymphoid cell neoplasms should not be grouped with nonlymphoid neoplasms in determining the toxicity and carcinogenicity of test substances.

Spontaneous neoplasms in aged CD-1 mice.

Spontaneous neoplasms in untreated control CD-1 mice (725 males and 725 females) used in carcinogenicity studies were evaluated and tabulated. The most common neoplasms in male mice were alveolar-bronchiolar adenomas (19.3%) followed by hepatocellular adenomas (11.0%), lymphoreticular neoplasms (6.8%), hepatocellular carcinomas (5.7%), Harderian gland adenomas (2.9%), alveolar-bronchiolar carcinomas (2.5%), and testicular interstitial cell tumors (1.9%). In the females, the most frequently occurring neoplasms were lymphoreticular neoplasms (16.4%) followed by alveolar-bronchiolar adenomas (12.3%), uterine endometrial polyps (4.3%), uterine leiomyomas (3.5%), mammary adenocarcinomas (2.5%), hepatocellular adenomas (1.8%), hemangiomas (1.7%), Harderian adenomas (1.7%), alveolar-bronchiolar carcinomas (1.5%), and pituitary adenomas (1.1%). Tumors in other various organs were found at a low incidence.

Spontaneous neoplasms in B6C3F1 mice

Spontaneous neoplasms in untreated B6C3F1 mice (200 males and 200 females) used as controls in 4 carcinogenicity studies were evaluated and tabulated. The most common neoplasms in male mice were hepatocellular adenomas/carcinomas (24.5%) followed by alveolar-bronchiolar adenomas/carcinomas (10.0%), lymphoreticular neoplasms (7.0%) [malignant lymphomas mixed (4.5%), histiocytic sarcomas (3.5%)], harderian gland adenoma (6.5%), and hemangiomas/hemangiosarcomas (5.5%). In the females, the most frequently occurring neoplasms were lymphoreticular neoplasms (22.0%) [malignant lymphoma mixed (10.0%), malignant lymphoma lymphocytic (6.5%), histiocytic sarcomas (5.5%)] followed by pituitary adenomas (15.5%), alveolar-bronchial adenomas/carcinomas (11.5%), hepatocellular adenomas/carcinomas (7.0%), harderian gland adenomas, uterine stromal polyps (2.5%), and hemangiomas/hemangiosarcoma (2.0%). The incidence of tumors in various other organs was found to be low.

Cloning of an apamin binding protein of vascular smooth muscle

The receptor for the bee venom derived neurotoxin, apamin, is widely believed to be an integral component of the small conductance calcium-activated potassium channel in many excitable cells. By affinity chromatography on immobilized apamin, a 78 kD apamin binding protein of the bovine brain synaptosomes was isolated. Antibodies were elicited against this protein and used to clone a cDNA from a porcine vascular smooth muscle expression library. This gene (Kcal 1.8) codes for a 438 amino protein with four potential transmembrane domains, one putative calcium binding site, a protein kinase C phosphorylation site, and a leucine zipper motif. Kcal 1.8 encoded protein has no significant sequence homologies with any known ion channels or receptors. Kcal 1.8 is likely to encode a protein associated with the small conductance calcium-activated potassium channel in vascular smooth muscle.

Incidence, Distribution, and Morphology of Amyloidosis in Charles Rivers CD-1 Mice

The incidence, morphology, and distribution of amyloidosis were reviewed in a 2-year toxicity-oncogenicity study in Charles Rivers CD-1 mice. Amyloid was present in the duodenum, jejunum, mesenteric lymph node, and ovary in animals sacrificed at 8 months. In animals sacrificed at 12 months, amyloid was also present in the adrenal gland, gall bladder, heart, ileum, kidney, pancreas, parathyroid, spleen, glandular stomach, testis, and thyroid. In the animals sacrificed at 24 months, the mammary gland was also involved. The organs most frequently involved at 24 months included the adrenal gland, duodenum, jejunum, ileum, heart, kidney, liver, mesenteric lymph node, ovary, spleen, and thyroid.

Spontaneously occurring leiomyosarcomas of the mouse urinary bladder.

Spontaneous leiomyosarcomas of the mouse urinary bladder have not been reported. Data from 8 chronic toxicity/oncogenicity studies that included 400 male and 400 female mice were reviewed and evaluated to gather information on spontaneously occurring urinary bladder leiomyosarcomas. Three control mice from 3 different studies had leiomyosarcomas in the submucosa of the trigone area of the urinary bladder. These tumors were not connected to the surface epithelium; however, they were connected to and destroyed the smooth muscle layer of the urinary bladder. This communication describes the incidence and histopatho-logical features of these neoplasms.

Non-neoplastic renal lesions in Sprague-Dawley and Fischer-344 rats

Incidences of non-neoplastic renal lesions in untreated Sprague-Dawley (1540) and Fischer-344 (491) rats were evaluated, tabulated, and compared. In Sprague-Dawley rats, the most frequently occurring lesion was chronic progressive nephropathy (68.5%) followed by tubular mineralization (30.9%), pelvic calculi (9.0%), brown pigmentation of the tubular epithelium (8.8%), hydronephrosis (5.1%), tubular dilatation (3.1%), and vascular mineralization (3.1%). In Fischer-344 rats, chronic progressive nephropathy (82.0%) was the most commonly occurring lesion followed by tubular mineralization (38.8%), vascular mineralization (2.2%), hydronephrosis (1.6%), and pelvic calculi (1.4%). In both strains, other lesions were less frequent.

Spontaneous renal lesions in CD-1 and B6C3F1 mice

Incidence and pathology of naturally occurring renal lesions in CD-1 and B6C3F1 mice are evaluated, tabulated, and discussed. In CD-1 mice, most frequent non-neoplastic renal lesion was interstitial nephritis (72.6%) followed by amyloidosis (40.6%), mononuclear cell infiltration (23.6%), tubular mineralization (12.8%), cortical cysts (8.2%), hydronephrosis (6.7%), tubular dilatation (5.9%), and tubular degeneration/regeneration (4.7%). Cortical epithelial origin renal cell carcinomas were observed in one male (0.13%) and one female mice (0.13%). In B6C3F1 mice, most commonly occurring non-neoplastic renal lesion was mononuclear cell infiltration (29.8%) followed by tubular mineralization (11.3%), interstitial nephritis (6.8%), tubular vacuolization (4.5%), tubular degeneration/regeneration (2.5%), and cortical cysts (1.3%). Cortical cell adenoma was the only primary renal neoplasm which was observed in one female mice (0.16%). In both strains, other renal lesions were less frequent.

Spontaneous Primary Astrocytoma in the Spinal Cord of a Mouse and a Rat

A spontaneous astrocytoma was observed as an incidental finding in the thoracic spinal cord of a control Charles Rivers CD-1 female mouse from a 2 yr oncogenicity study. An astrocytoma was also observed in the lumbar spinal cord of a Charles Rivers Sprague-Dawley control, female rat from a 2 yr oncogenicity study. The mouse was clinically normal and was sacrificed at the end of the 2 yr study. The rat was killed at 512 days of age because of posterior paralysis.