No abstract available.
9,10-Dimethyl-1,2-benzanthracene* ; Tocopherols*

No abstract available.
9,10-Dimethyl-1,2-benzanthracene* ; Carcinogenesis* ; Hyperbaric Oxygenation* ; Submandibular Gland*

No abstract available.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Breast Neoplasms* ; Breast* ; Estrogens* ; Rats*

No abstract available.
9,10-Dimethyl-1,2-benzanthracene ; Animals ; Rats ; Submandibular Gland

PURPOSE: To understand the morphologic and molecular changes in carcinogen-induced breast tissues, DMBA (10-dimethy1-1,2 benzanthracene) was administrated in Sprague- Dawley female rats. MATERIALS AND METHODS: At 50 days of age, all experimental rats were given 20 mg DMBA by gastric intubation. Until the seventh week after DMBA administration, six rats were sacrificed every week, thereafter all tumors found during 20 weeks were removed every week. The morphologic changes were evaluated in routinely processed sections stained with H-E and with anti-smooth muscle actin antibody. Mutation of Ha-ras codons 12 and 61 was examined by ARMS (amplification refractory mutation system) method in frozen tissues. RESULTS: The epithelial cell proliferation of terminal end buds began 2 weeks after DMBA treatment and progressed to the 6th week, resulting in microscopic malignant tumor in one of the 7th weeks rats. The tumors were developed in 43 of 62 rats (69.4%); 8 benign lesions in 4 rats and 72 malignant tumors in 39 rats. Mutations in the 12th and 61th codon of Ha-ras gene were respectively found in 29.7% and 2.7% of preneoplastic breasts, 25% in benign lesions, 2.6% and 31.6% of malignant tumors. CONCLUSION: DMBA treatment in rats induced epithelial proliferation, then benign and malignant tumors through Ha-ras gene mutation, especially in codon 61 leading to cancer.
9,10-Dimethyl-1,2-benzanthracene* ; Actins ; Animals ; Arm ; Breast ; Codon ; Epithelial Cells ; Female ; Genes, ras ; Humans ; Intubation ; Rats*

PURPOSE: This study was carried out to investigate the effect of irradiation on the expression of proliferating cell nuclear antigen (PCNA) and apoptosis induction during the carcinogenesis in hamster buccal pouch. MATERIALS AND METHODS: Three months old Syrian golden hamsters were divided into control and 2 experimental groups. Hamsters in control group were left untreated on buccal pouchs. Twenty four hamsters were treated with 0.5% DMBA tri-weekly on the right buccal pouch. Forty eight hamsters were treated with 0.5% DMBA tri-weekly and irradiated with the dose of 5 Gy and 10 Gy at 6, 9, 12, 15 weeks after DMBA application. Resected buccal pouches were sectioned and examined for potential expression pattern of PCNA and apoptosis. RESULTS: The PCNA index was increased with the stages of buccal pouch epithelium carcinogenesis except the hyperplasia stage in control group (p<0.05). The irradiation did not effect on the PCNA index in the dysplasia and the carcinoma in situ stage, but in the hyperplasia stage, the PCNA index was increased with 10 Gy radiation and decreased in the carcinoma stage (p<0.05). The apoptotic index was significantly decreased from the carcinoma in situ stage and the lowest in the carcinoma stage. The apoptotic index was significantly decreased in the hyperplasia and dysplasia stage with the 5 Gy irradiation and significantly increased only in the carcinoma stage with the 10 Gy irradiation (p<0.05). CONCLUSION: The PCNA and apoptotic index were varied according to the irradiation period and dosage in each carcinogenesis stage.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Apoptosis* ; Carcinogenesis* ; Carcinoma in Situ ; Cricetinae* ; Epithelium ; Hyperplasia ; Mesocricetus ; Proliferating Cell Nuclear Antigen* ; Radiation Dosage

PURPOSE: Ovarian cancer is a common gynecologic malignancy and the leading cause of death in women. It is typically not diagnosed until it has reached the advanced stages. We performed this study to investigate the roles of the proteins related to the G1 cell cycle in ovarian carcinogenesis. MATERIALS AND METHODS: Immunohistochemistry and Western blot were used to analyse the expression of cyclin Dl and CDK4 in 7, 12-dimethylbenzanthracene- induced ovarian cancer in rats. RESULTS: The Cyclin D1 and CDK4 labelling index was significantly higher in the ovarian cancers than in the normal ovarian surface epithelium of rats. There was no difference among the cancer types. In Western blot analyses, the expression of cyclin Dl and CDK4 in the ovarian cancers was higher than that in the normal ovarian surface epithelium. A positive correlation was observed between the expressions of the CDK4 and Cyclin D1. CONCLUSION: The upregulation of cyclin Dl and CDK4 that occurs in DMBA-induced rat ovarian carcinogenesis is likely to be associated with tumor progression. Further studies are needed to investigate the role and function of cyclin Dl and CDK4 in human ovarian cancer.
9,10-Dimethyl-1,2-benzanthracene ; Animals ; Blotting, Western ; Carcinogenesis ; Cause of Death ; Cell Cycle ; Cyclin D1* ; Cyclin-Dependent Kinase 4 ; Cyclins* ; Epithelium ; Female ; Humans ; Immunohistochemistry ; Ovarian Neoplasms* ; Rats* ; Up-Regulation

BACKGROUND: In order to investigate the roles of p16 and Rb, their expression was evaluated in 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced ovarian cancers of rats. METHODS: DMBA-coated silk was inserted into both ovaries of 20 9-week-old Sprague-Dawley rats. The experimental period lasted 20 weeks. The tumor histology was classified and the expression of p16 and Rb in the ovarian tumors was analyzed by immunohistochemistry and Western blot. RESULTS: The p16 and Rb labeling index was significantly lower in the ovarian cancers than the normal ovarian surface epithelium of a rat. There were no differences among the cancer types. In Western blot analysis, the expressions of p16 and Rb in ovarian cancers were lower than those in normal ovarian tissue. No correlation was present between p16 and Rb. CONCLUSION: The abnormal expression of p16 and Rb occurs in DMBA-induced rat ovarian cancer and might be involved in carcinogenesis.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Blotting, Western ; Carcinogenesis* ; Epithelium ; Female ; Immunohistochemistry ; Ovarian Neoplasms ; Ovary ; Rats* ; Rats, Sprague-Dawley ; Retinoblastoma Protein ; Silk

Cellular transforming genes have been identified in a number of different tumor cell lines and tumor types. A significant number of these oncogenes belong to the ras gene family. The ras gene family consists of three closely related genes:H-ras, K-ras and N-ras which code for a related 21 kDa protein. Mutations in codon 12, 13 and 61 of one of the three ras genes convert these genes into acute oncogenes. The presence of H-ras gene mutaions has important prognostic implication in various tumors. Each genomic DNA was isolated from tumors induced by implantation with DMBA, or by treatment with DMBA-implantation/irradiation. When genome DNA was transfected into NIH 3T3 cells and investigated by two-step PCR-RFLP, the following results were concluded : 1. Transformation foci developed in two groups when the genome DNA of two experimental groups were transfected into NIH 3T3 cells. 2. Transformation efficiency was 0.01-0.02 foci/ DNA in the experimental group with the DMBA-implantation, 0.01-0.03 foci/ DNA in the experimental group with the DMBA-implantation/irradiation according to results of trasfection assay. 3. When the point mutation of H-ras gene was investigated by a two-step PCR-RFLP, there was 13.9%(5/36) in the experimental group with the DMBA implantation, 15.4%(6/39) in the experimental group with the DMBA-implantation/irradiation. 4. The point mutation in codon 12 and 61 of H-ras was 5.6%(2/36) and 8.3%(3/36) in the experimental group with the DMBA implantation. 5. The point mutation in codon 12 and 61 of H-ras gene was 7.7%(3/39) in the experimental group with the DMBA-implantation/irradiation.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Cell Line, Tumor ; Codon ; DNA ; Genes, ras* ; Genome ; Humans ; NIH 3T3 Cells ; Oncogenes ; Point Mutation ; Rats* ; Salivary Glands*

PURPOSE: The incidence of salivary gland tumor is approximately 2% among all head and neck tumors, of which malignant cases account for only about 5%. Much research has been performed in order to clarify the mechanism of oncogene activation, however salivary gland tumors remain understudied. We performed this study in order to characterize the ras gene in these tumors. MATERIALS AND METHODS: We treated white rats with 7, 12-dimethylbenz[a]anthracene (DMBA) and confirmed the occurrence of salivary gland tumors after ten to thirty weeks. Isolated genomic DNAs from tumor tissues were added to NIH 3T3 cells. In order to detect Ha-ras mutations, we performed a two-step PCR-RFLP and 7analyzed the mutated sequences. RESULTS: We induced salivary gland tumors by DMBA treatment in white rats. Isolated DNAs from the tumor tissues transformed the NIH 3T3 cells. Point mutations were observed in codons 12 and 61 of the Ha-ras oncogene. The total frequency of point mutations was 13.9% in DMBA-induced salivary gland tumors in rats. CONCLUSION: Our results demonstrate that a variety of cancers ras oncogene mutations were also found in salivary gland tumors. We confirmed that a point mutation of the Ha-ras oncogene in a DMBA-induced salivary gland tumor occurs at a frequency of 13.9%.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Codon ; DNA ; Genes, ras* ; Head ; Incidence ; Neck ; NIH 3T3 Cells ; Oncogenes ; Point Mutation ; Rats* ; Salivary Glands*