In vivo enhancement of chemotherapy with static electric or magnetic fields.

We evaluated the ability of both static electric and static magnetic fields to enhance the in vivo action of a chemotherapeutic agent, adriamycin, against transplanted mammary tumors in mice. Female B6C3F1 mice with transplanted mammary adenocarcinoma were divided into four randomized groups and injected with 10 mg/kg adriamycin on day 7 of the study. Three of the groups were then exposed to nonuniform static electric or static magnetic fields. The resulting tumor regression in each group was measured four times during the remaining 13 days of the 20 day study. Two-sided statistical tests revealed all of the static field exposed groups achieved significantly greater (P

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 metastasizing mucinous adenocarcinoma in the ileum of a Sprague-Dawley rat.

Spontaneous tumours of the rat small intestine are extremely rare. A control Sprague-Dawley male rat from a carcinogenicity bioassay had a mucinous adenocarcinoma in the ileum. Tumour metastasis was observed in the mesenteric lymph node, lung, and seminal vesicles. Gross and histopathological features of this neoplasm are described and discussed.

Dietary restriction from middle age attenuates age-associated lymphoma development and interleukin 6 dysregulation in C57BL/6 mice.

Dietary restriction (DR) started in middle age profoundly reduces the occurrence of lymphoma in C57BL/6 mice. Here, we report immunocellular and molecular changes associated with this mode of cancer prevention. Twelve-month-old male C57BL/6 mice were either fed a control diet or subjected to moderate DR (approximately 25% < control intake). DR significantly reduced lymphoma development (incidence at 25 months, 19% of 72 control mice versus 5% of 60 DR mice). Flow cytometry of splenocytes showed that DR increased the percentage of CD4+ and CD8+ cells. Lymphomatous spleens displayed varied labeling patterns and high percentages of cells in S phase. Splenocyte c-myc expression tended to increase with age in controls and was reduced by DR. Lymphopenia and markedly reduced nucleated cell yields from peripheral lymphoid tissues were induced by DR. Serum interleukin 6 levels increased with age and were quite high (> 2500 pg/ml) in several mice with lymphoma and other histopathological findings. DR attenuated this age-associated increase. Immunohistochemical studies of lymphomatous spleens showed the presence of interleukin 6 in monocytic appearing cells but not in lymphoma cells. These observations support the possibility that an age-associated interleukin 6 dysregulation is important in lymphomagenesis.

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 ovarian choriocarcinoma, yolk sac carcinoma, and teratoma in B6C3F1 mice: a case report.

Three ovarian neoplasms (choriocarcinoma, yolk sac carcinoma, and teratoma) were diagnosed in a 2 yr carcinogenicity study involving B6C3F1 mice. The yolk sac carcinoma and the teratoma occurred in opposite ovaries of a single female mouse that was sacrificed in extremis on study day 725. The choriocarcinoma occurred in a female mouse that was sacrificed in extremis on study day 565. These neoplasms were considered to be spontaneous in origin.

Immunohistochemistry and morphology of reactive lesions in lymph nodes and spleen from rats and mice.

The use of immunohistochemistry with anatomical and systematized classifications of nonneoplastic lesions in hematopoietic pathology of lymph nodes and spleens from rats and mice is described. Polyclonal antisera and monoclonal antibodies to leukocyte and other antigens can be used with frozen or fixed tissue sections to identify changes in cell populations in these tissues in response to tissue injury and aging. A classification for reactive lesions of lymph nodes and spleen is proposed that can be utilized for computerized pathology and toxicology data systems. These classifications are based on a systematized anatomic distribution of the lesions with the aid of immunohistochemistry. The association of some lesions with early leukemia or lymphoma of rats and mice is also discussed.

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.

Histiocytic sarcoma in an aging gerbil.

A histiocytic sarcoma in an aging female gerbil is described. The neoplasm primarily involved the spleen and liver, and these organs were considered the primary sites of neoplastic origin. No neoplastic infiltration was noted in the uterus or ovaries as is commonly seen in the female mouse. This is the first report of histiocytic sarcoma in gerbils.

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 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 histopathological features of these neoplasms.

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.