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Biomedical subjects

C H Frith

Publications and source records attributed to C H Frith.

At least 55 records · Page 3Linked to original sources

Spontaneous lesions in virgin and retired breeder BALB/c and C57BL/6 mice.

Prevalences of neoplastic and nonneoplastic lesions were reported for 3,000 virgin and 800 retired breeder BALB/c and C57BL/6 mice, untreated and of both sexes. The most common nonneoplastic lesions in the BALB/c mice were: hepatic fatty metamorphosis, uterine hemosiderosis and mineralization, testicular atrophy, ovarian cysts, and adrenal subcapsular spindle cell hyperplasia. The most common neoplasms in the BALB/c mice were: pulmonary tumors, hepatocellular neoplasms, Harderian adenomas, and uterine polyps. Common nonneoplastic lesions in the C57BL/6 mice were: pulmonary lymphoid accumulations, hepatic fatty metamorphosis, multifocal aggregates of mononuclear cells in the liver, proteinaceous renal casts, uterine hemosiderosis, endometrial cystic hyperplasia, ovarian atrophy, ovarian cysts, and pituitary cysts. The most common neoplasms in the C57BL/6 mice were angiosarcomas and pituitary adenomas. Hematopoietic tumors were common in both strains.

Age Factors↗

Sequential morphogenesis of urinary bladder tumors in BALB/c mice given 2-acetylaminofluorene.

The sequential morphogenesis of bladder tumors induced in mice with 2-acetylaminofluorene were studied in order to understand better the morphogenesis of bladder tumors in humans. The study indicated 2 distinct patterns in the sequential morphogenesis. The first was a focal neovascularizaton of the transitional epithelium resulting initially in exophytic nodules which appeared more likely to develop into papilloma. The second was a nodular downgrowth of the transitional epithelium resulting initially in endophytic tumors which progressed to endophytic and exophytic carcinomas. Further work is needed to explain the significance of the 2 separate pathways which sometimes led to the same end result.

2-Acetylaminofluorene↗

Correlation of urothelial morphologic characteristics with the development of bladder carcinomas in BALB/c female mice administered 2-acetylaminofluorene.

Urinary bladders from 6909 of 24,172 control or 2-acetylaminofluorene (2-AAF) treated female BALB/c mice were examined histopathologically. Dietary doses of 2-AAF ranged from 75 to 150 p.p.m. for up to 33 months. Urinary bladder epithelial hyperplasia, vacuolization, and inflammation were frequent observations in treated animals and showed a positive correlation with dose level and length of administration of 2-AAF. Concretions were infrequently found and occurred only in controls. Squamous metaplasia, ulceration, and lymphocytic accumulations were infrequently noted but gave some indication of a positive correlation with 2-AAF dose level. Vacuolization was always associated with hyperplasia and/or bladder tumors. Observations on the concurrence of hyperplasia, vacuolization, and neoplasia suggest that both hyperplasia and vacuolization may be precursors of neoplasia. While inflammation was infrequently noted in non-tumor-bearing animals, greater than 90% of the time it was seen in association with tumors and appears to be a response of the bladder to tumor progression.

2-Acetylaminofluorene↗

A morphologic classification and incidence of alveolar-bronchiolar neoplasms in BALB/c female mice.

Lungs from 505 (21.1%) of 2,397 untreated control female BALB/c mice examined at various age intervals up to 1,001 days contained alveolar-bronchiolar neoplasms. Tumors were evaluated for histomorphological type, degree of differentiation, and size. Most of the tumors (286 of 505 or 56% of those examined) were of the papillary type and 450 of 505 (89.1%) were well differentiated. The incidence of the solid type and the well differentiated tumors was highest in the smallest size group (less than 0.5 mm) while that of the papillary and mixed types and the moderately and poorly differentiated tumors was highest in the larger size groupings. One hundred twenty-seven of 131 (97%) of all solid tumors were well differentiated while a lower percentage of papillary and mixed types (86.7% and 85.2%, respectively) were well differentiated. The mean age of mice with tumors from each histomorphological type, degree of differentiation, and size grouping also was determined.

Age Factors↗

Spontaneous hepatocellular neoplasms and hepatic hemangiosarcomas in several strains of mice.

The incidence of spontaneous liver tumors, ratio of hepatocellular adenomas to carcinomas, degree of differentiation of hepatocellular carcinomas, and incidence of pulmonary metastases in several strains of mice from different experiments were examined. Hepatocellular tumors were rare in all strains before 12 months of age and then increased with age. They were more common in male than in female mice. Pulmonary metastases were rare before 24 months of age and occurred in 10 of 221 mice with hepatocellular carcinomas (4.5%); their incidence in different strains was not strikingly different. Hepatic vascular tumors were less common than hepatocellular tumors. No tumors of bile duct origin were observed in these mice.

Age Factors↗

Osteosarcomas in BALB/c female mice.

Osteosarcomas were found in 16 of 24,192 (0.066%) BALB/c female mice, 14 were in 21,816 (0.064%) 2-acetylaminofluorene-treated mice, and two were in 2,376 (0.084%) untreated controls. The osteosarcomas were classified into osteoblastic, fibroblastic, and mixed types. Seven of the osteosarcomas metastasized to the lungs. The osteosarcomas in control and 2-acetylaminofluorene-treated mice showed little or no difference in the incidence, type, size, or site of origin, indicating that 2-acetylaminofluorene did not affect the development of osteosarcomas in BALB/c female mice.U

2-Acetylaminofluorene↗

Morphologic classification and correlation of incidence of hyperplastic and neoplastic hematopoietic lesions in mice with age.

Information from the NCTR control pathology data base was examined to morphologically classify and correlate the incidence off hyperplastic and neoplastic hematopoietic lesions with age in over 15,000 male and female mice of a variety of strains. Hyperplasia affected lymphoid and reticular cells, erythropoietic and granulopoietic cells, mast cells, plasma cells and megakaryocytes. Neoplastic lesions included lymphocytic lymphoma, mixed cell lymphoma, histiocytic lymphoma, granulocytic leukemia, plasma cell neoplasms and mast cell neoplasms. Most hyperplastic and neoplastic hematopoietic lesions increased wtih age and most were slightly more common in the female than in the male mice.

Aging↗

Toxicology in mice of the antileukemic agent 5-aza-2'-deoxycytidine.

The toxic effects of 5-AZA-2'-deoxycytidine (5-AZA-CdR) administered as a 12 hr. i.v. continuous infusion to CD2F1 (Balb/c x DBA/2) mice were investigated. This i.v. route of administration of 5-AZA-CdR was chosen because it produced a potent antineoplastic effect in leukemic mice and would probably be the route used for clinical trials of this agent. The LD50 of 5-AZA-CdR for male and female CD2F1 mice was estimated to be 29.5 and 22.2 mg/kg, respectively. A toxic dose of 5-AA-CdR produced a leukopenia, thrombocytopenia, and weight loss in the mice. Most of these toxic effects were reversible with the exception of leukopenia which was still present 43 days after the infusion. Histopathological analysis of the mice during the acute toxic phase (day 7) and the recovery period (day 28) showed that 5-AZA-CdR at a dose close to the LD50 produced bone marrow hypoplasia, necrosis of the small intestinal mucosa and atrophy of thymus and testes. All these pathological lesions were reversible. The toxic effects produced by 5-AZA-CdR are consistent with its biological action, an agent that is cytotoxic to only proliferating cells.

Animals↗

Incidence of pulmonary metastases for various neoplasms in BALB/cStCrlfC3H/Nctr female fed N-2-fluorenylacetamide.

Incidence of pulmonary metastases for a variety of neoplasms was studied in many inbred BALB/cStCrlfC3H/Nctr female mice fed 2-fluorenylacetamide. Bladder carcinomas and hepatocellular carcinomas appeared to be the only neoplasms that were dose related. Hepatocellular carcinomas metastasized to the lungs at an incidence of 4.8%, and bladder carcinomas metastasized at an incidence of 0.28%. Osteogenic sarcomas metastasized to the lungs at an incidence of 46.2%; renal adenocarcinomas, at 20%; fibrosarcomas, at 16.7%; mammary adenocarcinomas, at 9.8%; and myoepitheliomas, at 10.5%. Other malignant neoplasms, including leiomyosarcomas, granulosa cells tumors, adrenocortical carcinomas, angiosarcomas, squamous cell carcinomas, and harderian gland tumors, metastasized at an incidence of less than 5%.

2-Acetylaminofluorene↗

A morphologic classification and incidence of spontaneous ovarian neoplasms in three strains of mice.

Ovarian tumors were reviewed and classified in 5,404 control inbred BALB/c, C57BL/6, and C3H mice. In descending order of frequency, the most common types in the C3H mice were the tubular mesothelioma (adenoma), thecoma, luteoma, granulosa cell tumor, and cystadenoma. In descending order the most common types in the BALB/c mice were the luteoma, tubular mesothelioma, granulosa cell tumor, thecoma, and cystadenoma. The tubular mesothelioma was the only ovarian tumor of significance in the C57BL/6 mice. Most of the ovarian tumors were rare before 1 year of age, but they increased with age after 1 year.

Animals↗

A scanning and transmission electron microscopic study of urinary bladders of mice treated with 2-acetylaminofluorene.

Urinary bladders of BALB/c male mice treated with 250 ppm of 2-acetylaminofluorene for 1, 3, 5, 7, and 14 days were examined for early scanning (SEM) and transmission electron microscopic (TEM) changes. SEM observations at days 1, 3, and 5, and TEM observations at days 1 and 3 revealed no significant changes. The bladders of the mice treated for 7 days contained an occasional focus showing irregularity in the shape and size of the superficial cells and SEM revealed ropey microridges in an occasional cell. The bladders of mice treated for 14 days had a greater irregularity of cell size on SEM. TEM changes were evident as early as 5 days with an increase in severity at 7 and 14 days. A numerical reduction of fusiform vesicles, asymmetric membrane plaques and Golgi apparatus along with an increase in membranous whorls, endoplasmic reticulum, cytolysosomes, and small rounded vesicles was evident. The study may aid in a better understanding of early morphologic changes of urothelium in response to a carcinogen.

2-Acetylaminofluorene↗

Comparison of experimental and spontaneous bladder urothelial hyperplasias occurring in BALB/c mice.

Spontaneously occurring hyperplasia of urothelium of mice was compared morphologically to hyperplasia induced with 2-acetylaminofluorene (2-AAF) and 4-ethylsulfonylnaphthalene-1-sulfonamide (ENS). Simple and nodular hyperplasias were seen in all groups. Nodular downward hyperplasia was more commonly located in the vertex of the bladder of the 2-AAF treated mice but was more commonly located in the neck region of the ENS and control mice. The 2-AAF induced hyperplasia appeared to be capable of regression or progression to neoplasia. The ENS induced and the spontaneously occurring downward hyperplasia appeared to be secondary to a chronic cystitis and did not appear to progress to neoplasia.

Animals↗