Journal of Pathology and Translational Medicine

Original Articles

The Relation between Cell Proliferation and Apoptosis According to the Histologic Types in Chemically Induced Rat Mammary Tumorigenesis.: Tae Jung Jang, Woo Hee Jung, Kwang Gil Lee; Korean J Pathol. 1998;32(3):174-185.

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Abstract PDF: Balancing the rates of cell proliferation and cell death is important in maintaining normal tissue homeostasis. The relationship among apoptosis, cell proliferation and factors influencing apoptosis according to the histologic types in chemically induced mammary tumorigenesis appears important in understanding the pathogenesis of breast carcinoma. In this study, we investigated alterations in the kinetics of cell proliferation and apoptosis during rat mammary tumorigenesis induced by 7, 12-dimethylbenzanthracene (DMBA) and we related these changes to the expressions of bcl-2, p53, and TGF-beta. Seven-week-old female Sprague-Dawley rats were divided into an experimental group (20 mg/ml DMBA by oral intubation) and a control group. The results were as follows. 1. In the experimental group, breast tumors occurred in twenty two of fifty nine rats(37.3%, 22/59), and the total number of tumors was 100 (4.5 2.0/rat). The histological classification was infiltrating ductal carcinomas (n=5), ductal carcinomas with focal invasion (n=10), intraductal carcinomas (n=36), adenomas accompanied with intraductal proliferation (n=35), intraductal proliferation (n=9), and adenomas (n=5); 2. The differentiation of terminal end bud into alveolar bud (AB) in the experimental group was significantly lower than that of the control group (p<0.05); 3. BrdU labeled tumor cells were mainly located at the peripheral portion of tumor cell nests. BrdU labeling indices were highest in ductal carcinomas, less pronounced in intraductal proliferation, and lowest in adenomas, whereas apoptosis levels were highest in adenomas, less pronounced in intraductal proliferation, and lowest in ductal carcinomas (p<0.05); 4. p53 protein was not expressed in any breast tumors. Although the expression of bcl-2 protein was highest in infiltrating and focal infiltrative ductal carcinomas (58.3%), compared with adenomas, intraductal proliferation, and intraductal carcinomas (p<0.05), the extent of its expression was less than 1% of all tumor cells; 5. TGF-beta was mainly expressed in the central portion of tumor cell nests rather than in peripheral portion, and TGF-beta immunoreactive tumor cells displayed good differentiation and did not reveal BrdU immunoreactivity. TGF-beta labeling index of infiltrating and focal infiltrative ductal carcinomas was significantly higher than that of intraductal carcinomas, intraductal proliferation, and adenomas (p<0.05). Based on these results, it is thought that high cell proliferation and the suppression of apoptosis are closely associated with DMBA-induced rat mammary carcinogenesis. However, the suppression of apoptosis is not related to p53 mutation, bcl-2, and TGF-beta. TGF-beta seems to be reversely related to tumor cell proliferation but closely associated with the progression of the tumor, especially an invasion of breast carcinomas.

Evaluation of Prognostic Significance of AgNORs and PCNA during 9,10-dimethyl-1,2-benzantracene(DMBA)-induced Hamster Buccal Pouch Carcinogenesis.: Sam Pyo Hong, Myong Soon Song, Seong Doo Hong, Jae Il Lee, Chang Yun Lim; Korean J Pathol. 1998;32(5):337-345.

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Abstract: The purpose of this study is to evaluate the prognostic significance of argyrophilic nucleoalr organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA) by using DMBA hamster buccal pouch carcinogenesis which provides a good experimental model in reproducing steps from precancerous lesions to invasive squamous cell carcinomas. The buccal pouches of 50 Syrian hamsters were applied with 0.5% DMBA in mineral oil three times a week to reproduce various lesions from precancerous ones such as hyperkeratosis or epithelial dysplasia to invasive squamous cell carcinomas. Their sections were stained with H & E, and silver colloid, and processed immunohistochemically by being applied with monoclonal antibody to PCNA. The histopathologic examainations were done and the counts of AgNORs were evaluated. The PCNA labelling indices on each lesions were evaluated. The correlation between histopathological grades and counts of AgNORs or PCNA labelling indices were evaluated. The number of AgNORs was 2.22+/-0.22 in control group, 3.46+/-0.72 in carcinoma in situ (CIS), 3.78+/-0.63 in squamous cell carcinoma (SCC), respectively. AgNORs significantly increased in severe epithelial dysplasia, CIS, and SCC compared with normal tissue (P<0.05). The PCNA Labeling Index (LI) was 39.47+/-6.68% in control group, 79.61+/-4.14% in CIS, and 85.43+/-6.25% in SCC, respectively. PCNA LI also significantly increased in epithelial dysplasia, CIS, and SCC compared with normal tissue (P<0.05). The number of AgNORs, AgNOR area, and PCNA LI slightly increased in the advancing front than in the center of SCC, but, it was not statistically significant. It appeared that there were a good correlation between the number of AgNORs and PCNA LI (Pierson correlation coefficient : 0.649, P<0.001). These results suggested that the number of AgNORs and the PCNA LI could be useful markers for evaluating the risk of malignant transformation and prognosis of SCC. It was thought that the clinical usefulness of these markers should be verified by using human tissue specimens.

DNA ploidy and Cellular Proliferation Activity in Experimentally Induced Malignant Fibrous Histiocytoma.: Ji Shin Lee, Jong Tae Park, Sang Woo Juhng, Hong Ran Choi, Kyu Hyuk Cho; Korean J Pathol. 1993;27(3):205-216.

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Abstract PDF: To fine out the changes of DNA ploidy and cellular proliferation activity during carcinogenesis and evaluate correlation between flow cytometrically determined S-phase fraction and proportion of proliferation cell nuclear antigen(PCNA, PC10) immunoreactive cells, the authors studied on malignant fibrous histocytoma induced by intra-articular injection of 9, 10-dimethy1-1, 2-benzanthracene(DMBA) in the rats. Forty Wistar rats were used. The results obtained were as follows. 1) Firstly, tumors were palpated 5 weeks after the last injection of DMBA and formed in 27 rats at sacrificed. Histologically, these lesions showed storiform, indicative of malignant fibrous histiocytoma. 2) Three cases of DNA aneuploidy were observed at 4 and 5 months after the last injection of DBMA and one of them, which was DNA diploidy at main mass, was found at daughter mass. 3) Flow cytometrically determined S-phase fraction and proportion of PCNA(PC10) immunoreactive cells in malignant fibrous histiocytoma induced by DMBA were much higher than in control groups and slightly increased according to sequential changes after formation of mass. The comparison of flow cytometrically determined S-phase fraction and proportion of PCNA(PC10) immunoreactive cells showed significant correlation(r=0.6092, p<0.001). Above results strongly suggest that ploidy pattern may evolve into aneuploid type during the development of tumor and proliferation activity increases during the carcinogenesis.

A Study on the Precancerous Lesion of Breast Carcinoma in 9, 10-Dimethyl-1, 2-Benzanthracene-treated Rats.: Cheon Sik Choi, Soo Min Kang, Hye Jung Lee, Gyung Hyuck Ko, Cheol Keun Park; Korean J Pathol. 1991;25(2):104-113.

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Abstract PDF: Following results were obtained from the light microscopic and stereomicroscopic observations of the breasts of rats treated with 9, 10-Dimethyl-1,2-Benzanthracene(DMBA). 1) Adenocarcinomas developed in 17 rats (24%) among 70 DMBA-treated rats. 2) Terminal and buds (TEB) were observed longer in DMBA-treated rats than in control group, but they finally disppeared 4 monthes after treatment. 3) Many hyperplastic alveolar nodules (HAN) developed in DMBA-treated rats. 4) There were no transitional lesions between TEB and adenocarcinoma or HAN and adenocarcinoma. 5) The number of lobules was decreased in DMBA-treated rats. On the other hand, terminal ducts were increased in number. These findings suggest that DMBA stimulate the regression of lobules and induce to form terminal ducts from which adenocarcinomas and HAN develop independently.

An Experimental Study of DMBA (9,10-Dimethyl-1,2-Benzanthracene) Induced Knee Joint Tumors in the Rats.: Myung Jae Kang, Dong Geun Lee, Sam Im Choi, Sang Ho Kim; Korean J Pathol. 1988;22(4):424-434.

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Abstract PDF: For the morphological analysis of DMBA (9,10-diemethyl-1,2-benzanthracene) induced tumor, thirty Sprague-Dawley rats were received 0.1 ml of a 2% paraffin solution of DMBA into the knee joint cavity, which was repeated three times at an interval of 4 weeks. The induced tumor masses were removed at the 12th week after the first injection. Histological and histochemical examinations (H & E, PAS, alcian blue, Van Gieson, prussian blue, reticulin, PTAH stain) and enzyme histochemical examinations (acid phosphatase, alkaline phosphatase, alpha-naphthyl acetate esterase) were performed. The results were as follows: 1) By the 12th week after the first injection of DMBA, the tumor incidence rate was 20 percent. 2) On histological and histochemical examination, most of the induced tumor disclosed the features of the fibrous histiocytoma originating from mesenchymal cells, and the remains sweat gland adenoma and adenocarcinoma originating from epithelial cells. 3) On enzyme histochemical examination, most of the mesenchymal cell-derived tumor cells showed positive reactions for acid phosphatase and alpha-naphthyl acetate esterase, which were similar characteristic features of enzyme stains as shown in the component cells of fibrous histiocytoma.

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