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Biomedical subjects

C H Frith

Publications and source records attributed to C H Frith.

At least 73 records · Page 4Linked to original sources

The effects of ascorbic acid on the induction of urothelial lesions in mice by 2-acetylaminofluorene.

288 BALB/c male mice were allocated to: Group 1-control; Group 2-500 ppm of 2-acetylaminofluorene (2-AAF) in the food, with control water; Group 4-500 ppm of 2-AAF in the food and 250 mg/100 ml of vitamin C in the water; and Group 3-control food and 250 mg% of vitamin C in the water. Major histopathologic changes at the end of 28 days included both inflammation of the lamina propria and hyperplasia of the transitional epithelium of the urinary bladder in mice receiving 2-AAF. The most severe lesions were seen in the mice administered the combination of 2-AAF and vitamin C. It was postulated that either decreased water consumption and concentration of the urine and/or reduction in urinary pH may have contributed to the severity of the lesions.

2-Acetylaminofluorene↗

Correlations between gross and microscopic lesions in carcinogenic studies in mice.

Microscopic diagnoses of a number of spontaneous and induced neoplasms in mice were correlated with the gross findings of the ED01 and a number of other carcinogenic studies conducted at NCTR to determine the value of detailed histopathologic examinations in bioassay testing. The results indicated that for organs such as thymus, lung, adrenal, Harderian gland and urinary bladder 50% or more of the neoplastic lesions would be missed if at least one histological section were not examined from each organ. For organs such as the liver and mammary gland, a single tissue section did not greatly improve the ability to detect neoplastic lesions beyond that afforded by a thorough necropsy examination.

Adrenal Cortex Neoplasms↗

Biologic and morphologic characteristics of urinary bladder neoplasms induced in BALB/c female mice with 2-acetylaminofluorene.

2-Acetylaminofluorene (2-AAF) induced transitional cell carcinomas, transitional cell carcinomas with squamous metaplasia, squamous cell carcinomas and undifferentiated carcinomas in the urinary bladders of BALB/c female mice. The transitional cell carcinoma was the most common, but was less aggressive and infiltrative than the other three types. The carcinomas were most likely to occur in the vertex of the bladder. A positive correlation existed between dose and length of administration of 2-AAF and the incidence, type, depth of invasion, and the location of the bladder carcinoma.

2-Acetylaminofluorene↗

Biologic and morphologic characteristics of hepatocellular lesions in BALB/c female mice fed 2-acetylaminofluorene.

2-Acetylsaminofluorene (2-AAF) induced foci of hepatocellular alterations, hepatocellular adenomas, and hepatocellular carcinomas in BALB/c female mice. The incidence of basophilic cell foci decreased with high dose levels of 2-AAF, and the incidence of hepatocellular adenomas decreased with both high dose levels and length of administration of 2-AAF. The results suggest that the hepatocellular foci of cellular alteration may give rise to the hepatocellular adenomas which in turn may give rise to hepatocellular carcinomas. The study also suggests that both hepatocellular adenomas and carcinomas may develop de novo. Hepatocellular carcinomas rarely metastasized before 18 months, and the less differentiated hepatocellular carcinomas were more likely to metastasize. 2-AAF did not alter the incidence of spontaneous hemangiosarcomas.

2-Acetylaminofluorene↗

Automated and computer-assisted pathology support for a large chronic study.

Pathology support for the 24,192 mouse toxicological ED01 study at the National Center for Toxicological Research was provided by the University of Arkansas Pathology Services Project through a contract between NCTR and the University of Arkansas. To aid in the collection, storage, retrieval, and analysis of this large amount of data an automated computer-assisted pathology system was developed. Use of this system has resulted in accurate data, the ability to handle large amounts of data, and low-cost analysis of the data.

Animals↗

Analysis of life-shortening effects in female BALB/C mice fed 2-acetylaminofluorene.

A total of 4320 female BALB/cStCrlfC3H/Nctr mice were continuously fed 2-acetylaminofluorene (2-AAF) in the diet at various concentrations in order to obtain a quantitative assessment of dose-related life-shortening effects. Statistical procedures which adjust for extraneous deaths were used to analyze the survival data. In addition to the demonstration of a reduced survival time associated with bladder and liver tumors induced by 2-AAF, a further toxic effect was observed at 150 ppm. Since the experiment was replicated six times, variability in the survival times of animals in different replicates was studied. Although all replicates were conducted under specific pathogen free / defined flora (SPF/DF) conditions, a significant change in survival time was demonstrated across replicates.

2-Acetylaminofluorene↗

Estimation of distributions of time to appearance of tumor and time to death from tumor after appearance in mice fed 2-acetylaminofluorene.

A recently-developed statistical technique is employed to estimate parameters of the distributions of time to appearance of tumors and time to death from tumors after their appearance using both interval sacrifice and survival information. Estimates are obtained for three types of tumors at each of eight dose levels of 2-AAF, namely, 0, 30, 35, 60, 75, 100 and 150 ppm, which were administered to a total of 20880 female BALB/cStCrlfC3Hf/Nctr mice. For bladder neoplasms, the estimated median times to tumor ranged from 19.8 months at 150ppm to 1876.6 months at 0 ppm, while for liver neoplasms the extremes were 25.2 months at 150 ppm and 37.7 months at 0 ppm. Reticulum cell sarcomas occurred on the average at 24.7 months in all dose groups except 150 ppm, where the average time to appearance was 22.9 months. Although a pronounced dose-response for time-to-tumor was expressed for both bladder and liver neoplasms, the time required for death from either neoplasm following its appearance was not dose-related. The estimated median times to death after appearance of tumors were as follows: bladder neoplasm, 6.8 months; liver neoplasm, 5.7 months; reticulum cell sarcoma, 3.0 months.

2-Acetylaminofluorene↗

Morphologic characteristics of benign and malignant renal cell tumors in control and 2-acetylaminofluorene-treated BALB/c female mice.

A total of 108 mice with renal cell tumors were obtained from a total of 25,916 control and 2-AAF-treated BALB/c female mice. A total of 119 renal cell adenomas and 37 renal cell carcinomas from the 108 mice were classified morphologically. The 119 renal cell adenomas were divided into cystic (32%), cystopapillary (29%), papillary (24%), and solid (15%). The 37 renal cell carcinomas were divided into tubolosolid (16%), tubolopapillary (49%) and tubulopleomorphic (35%). Pulmonary metastases occurred only in the tubulopleomorphic adenocarcinomas. In mice having renal cell tumors and surviving less than 650 days, the renal cell carcinomas were usually multiple and renal cell adenomas often coexisted in the same kidney. In mice having renal cell tumors and surviving more than 650 days, the renal cell carcinomas usually consisted of single large tumors without coexisting renal cell adenomas. The results suggest that the renal cell adenoma may progress to renal cell carcinoma. The various dose levels of 2-AAF did not significantly affect the incidence of renal cell tumors.

2-Acetylaminofluorene↗

Hematologic and clinical chemistry findings in control BALB/c and C57BL/6 mice.

The normal ranges for a variety of hematologic and clinical chemistry findings in 1,540 control BALB/c and C57BL/6 mice of various ages was determined. The total leukocyte count for both strains was highest at 1-3 months of age, and it usually decreased slightly until the mice were 18 months old. Hemoglobin values decreased with age. In both strains, the values for phosphorous, calcium, alkaline phosphatase, and urea nitrogen decreased after 3 months of age and then increased after 12 months of age. Differences between sexes were present for one or both of the strains for hemoglobin, phosphorus, glucose, cholesterol, aspartate aminotransferase, total protein, albumin, and alkaline phosphatase.

Aging↗

Morphologic classification of inflammatory, nonspecific, and proliferative lesions of the urinary bladder of mice.

A morphologic classification of inflammatory, nonspecific, and proliferative lesions of the urinary bladder of mice has been developed. The system was developed over a period of several years in order to tabulate and summarize the lesions for review. The classification has successfully met the needs of the National Center for Toxicological Research and has also provided useful information in understanding the biologic significance of urothelial lesions in mice.

Animals↗

Computer-assisted collection and analysis of pathology data.

At the National Center for Toxicological Research, long-term experiments with mice requiring the collection, storage, retieval, and analysis of an inordinate amount of data necessitated the development of an automated pathology information system. The system included automatic collection of mouse body and organ weights and hematologic findings; the use of mark-sensitive forms for the collection of gross and microscopic findings; and the use of computers for the storage, retrieval, and analysis of pathology data.

Animals↗

Hepatic cytologic and neoplastic changes in mice given benzidine dihydrochloride.

The administration of benzidine dihydrochloride in water to mice for up to 39 weeks resulted in hemosiderosis of the spleen, focal vacuolization of the transitional epithelium of the urinary bladder, and chronic inflammation and cytologic and neoplastic changes in the liver. Basophilic and acidophilic cytologic foci appeared in the liver as two distinct entities and both appeared preneoplastic. Benign and malignant liver tumors were also seen. Both types of cytologic changes and malignant liver tumors were more common in the female than male mouse.

Aminobiphenyl Compounds↗

Advances in automation for experimental pathology.

The establishment of the National Center for Toxicological Research (NCTR), Jefferson, AR, to study long term effects of low doses of potentially toxic substances, including carcinogens, resulted in the initiation of chronic experiments requiring histophatologic studies of large numbers of animals. Processing the tissues and recording and analyzing the massive amount of pathologic data from these studies required innovative automated technics. The result was a unique computerized pathology data system of NCTR. The system encompasses the development of training programs for necropsy techincians, histology technicians, and pathology tissue screeners; the use of automated equipment for processing, embedding, sectioning, and staining tissue; the use of prelabeled cassettes, slides, and pathology forms; the use of mark-sensitive forms for the collection of gross and microscopic findings; the use of data collection terminals for animal identification, animal weights, and organ weights; the collection of gross and microscopic data on a Mod Comp III minicomputer; and the storage, analysis, and generation of pathology reports and tables over a data link from an IBM 370-158 computer. Some of the features of this system may be applicable in other toxicology laboratories and medical pathology departments.

Animals↗

Mast cell neoplasia in mice.

Gross and histopathologic findings were reported for mast cell neoplasia in 2 female BALB/cStCrIBR mice. Microscopic findings included neoplastic mast cells in the liver, spleen, kidney and lymph nodes. Neoplastic mast cells were present in the blood smear of one of the animals.

Animals↗

Alkaline phosphatase activity in hyperplastic and neoplastic urinary bladder epithelium of mice fed 2-acetylaminofluorene.

Studies were made on the urinary bladder of 66 BALB/c mice of both sexes; 21 were fed a normal diet and 45, a diet containing 100-500 parts per million (ppm) of 2-acetylaminofluorene (2-AAF). Bladder epithelial hyperplasia was noted in 22 of 24 mice given 2-AAF for 7 months and in 20 of 21 given 2-AAF for 19 months. Transitional cell carcinomas were in 12 of 21 mice given 2-AAF for 19 months and in all except the 9 females given the low dose (100 ppm). Special stains revealed marked alkaline phosphatase activity in the bladder epithelium of untreated controls and slightly to moderately reduced activity in the hyperplastic epithelium, particularly the lower layers, of mice given 2-AAF for 7 months. Activity was markedly reduced and confined largely to the upper layers in mice treated for 19 months. The transitional cell carcinomas showed no activity except focally in a few tumor masses in 11 of 12 mice with tumors. Alkaline phosphatase activity was usually slightly to moderately increased in the sub-epithelial stroma after 7 months' treatment with 2-AAF and markedly increased after 19 months. Loss of alkaline phosphatase activity in the bladder epithelium may be a preneoplastic change.

Alkaline Phosphatase↗