• Environmental Mutagens and Carcinogens
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• v.9 no.1
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• pp.1-12
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• 1989

To study the selective organospecific carcinogenesis by the specific chemical carcinogens, the breast cancer induction model by oral administration of 7, 12-dimethylbenzanthracene (DMBA) or by intravenous injection of N-methylni-trosourea (NMU) on female rats was analyzed. In the present experiment, we compared the effexts of ages on the chemical mammary carcinogenesis by studying the metabolic system of the carcinogenic activation, detoxification or DNA damage and repair. The breast tumor incidence was significantly higher in the young rats of 50 days old than in those of one year old rats. As an index of organospecific DNA damage or repair, the in vivo covalent binding index(CBI) of the specific organs by the specific chemical carcinogens was monitored. And for the analysis of carcinogenic activation, the quantity of cytochrome P450`s was determined with the respective type-specific monoclonal antibody, while the detoxication capacity was deduced by the activity monitoring of glutathione S-transferase (GST) and peroxidase. The skin tissues of the mammary region had the highest CBI with both of DMBA and NMU at 50 days of age. And there were contrasting differences in the contents of carcinogenic activation and detoxication system: that is, the content of T.C.D.D.-inducible cytochrome P450 was high, while the activities of GST and peroxidase was low in the mammary skin tissues at tumor prevalent age. These results led us to conclude that the molecular organospecific carcinogenesis, as illustrated with mammary carcinoge-nesis by DMBA and NMU, is operated probably through the differential capacity of the target tissues in the high carcinogenic activation, low detoxication and the low DNA repair function.

• The Journal of the Korean bone and joint tumor society
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• v.20 no.1
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• pp.1-6
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• 2014

Purpose: To examine the expression of Connective Tissue Growth Factor (CTGF) in osteosarcoma and to evaluate its role in osteosarcoma invasion and proliferation. Materials and Methods: The mRNA expression of CTGF from 23 patient-derived osteosarcoma cell lines was examined, and the role of CTGF in cell invasion and proliferation was examined using siRNA transfection. Results: The over-expression of CTGF mRNA was observed in 17 cell lines (74%). CTGF-specific siRNA transfection into SaOS-2 and MG63 cell lines resulted in efficient knockdown of CTGF expression on Western blot analysis. siRNA transfected cells showed decreased migration on Matrigel invasion assay and decreased cell proliferation on WST-1 assay. Conclusion: These results indicated that the CTGF expression may play an important role in osteosarcoma progression, and may be a therapeutic target of osteosarcoma.

• Korean Journal of Bronchoesophagology
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• v.3 no.2
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• pp.199-208
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• 1997

• Korean Journal of Bronchoesophagology
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• v.3 no.2
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• pp.234-244
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• 1997

• Korean Journal of Bronchoesophagology
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• v.3 no.2
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• pp.226-233
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• 1997

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.126-126
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• 1993

암을 유발시키는 원인은 생물, 물리, 화학적 요인 등 여러 가지가 있으나 근자에 들어 산업후에 따르는 환경오염의 증가는 화학적 원인에 의한 발암가능성을 증대시키고 있다. 이러한 화학적 인자의 발암 기전 중 많은 부분이 유전자에 상해를 일으킴으로써 암을 발생시킨다고 알려져 있다. 그러므로 항암실험을 수행하였던 파푸아뉴기니아산 열대식물 13과 23종 부위별 36시료에 대하여 항변이원성 검색실험을 통하여 유전독성을 가진 화학적 요인에 의한 발암 가능성에 대한 예방 효과를 알아봄으로써 발암에 대한 예방약물 개발의 기초 자료를 제공하고자 본 실험을 수행하였다.

• Journal of Chest Surgery
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• v.36 no.9
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• pp.666-673
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• 2003

Cigarette smoking is the leading cause of the lung cancer. However, mechanism of action underlying the carcinogenesis in the lung still remains to be elucidated. The present study attempted to look into the carcinogenic potential of tobacco-specific nitrosamine, NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) and the effects of protein kinase C (PKC) isoforms in an immortalized human epithelial cell model. Material and Method: Immortalized human epithelial cells were exposed with NNK and examined for its carcinogenic potential as measured by saturation density, soft-agar colony formation, and cell aggregation assay. The specific isoform of PKCs involved in the cellular transformation was analysed through western blot with monoclonal antibody and measured separately in cytosolic fraction and membrane fraction. Result: Human epithelial cells exposed with NNK showed prominent carcinogenic potential in saturation density, soft agar colony formation, and cell aggregation assay. PKC isoform analysis results are as follows: PKC- $\alpha$ showed significant translocation of protein levels from cytosolic fraction to membrane fraction, as analyzed by immunoblot. PKC- $\varepsilon$ showed a dose-dependent increase of translocation. PKC- λ was not affected by NNK treatment. Conclusion: The study demonstrated that there was a certain specificity in the patterns of isoform induction following chemical carcinogen exposure. Thus, it is suggested that identification of specific isoform be a clue to find target molecules in the carcinogenesis.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 1996.12a
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• pp.16-18
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• 1996

• Parasites, Hosts and Diseases
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• v.32 no.1
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• pp.13-18
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• 1994

Chronic Clonorchis sinensis (CS) infection Is etiologically related to cholangiocarcinoma (CHCA) in human and animals. This study was carried out to clarify the role of CS Infection on dimethylnitrosamine (DMN)-induced cholanglocarcinogenesis. Fifteen hamsters were administered with 15 ppm DMN for 4 weeks and one week later, the hamsters were infected with 15 metacercariae of CS (DMN→CS group). The other 15 hamsters were infected with CS and after 5 weeks they were treated with the drug, praziquantel. Again one week later, the hamsters were administered with DMN (CS→DMN group). The other IS hamsters were adulnistered with DMN and CS simultaneously (CS + DMN group) . Histopathological examination of the livers showed CHCA with papillary or adenomatous hyperplasia of bile ductules in 3 of 15 hamsters of DMN→CS group and in 11 of 15 hamsters of DMN + CS group. These results suggest that CS infection to hamsters may have a promoting effect on the development of CHCA.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.23 no.4
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• pp.295-305
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• 2001

Protein kinase C (PKC) is known to play a pivotal role in neoplastic transformation cells and its high expression is often found in a variety of types of tumors including oral cancer. While PKC is associated with the altered signal transduction pathway of the tumor cells, it is still unclear which isoform is involved in the carcinogenesis process. Since the cellular distributions and the roles of PKC are isoform-specific, it is very important to identify the specific target molecules to improve our understanding of the carcinogenesis processes. Thus, the present study attempted to perform chemical carcinogen-induced neoplastic transformation of human epithelial cells and analyze the specific isoform of PKCs involved in the cellular transformation. The study analyzed overall PKC responses upon MNNG(N-Methyl-N'-nitro-N-nitroso guanidine) exposure with [$^3H$] PDBu binding assay. PKC translocation was observed at high doses of MNNG treatment in the presence of extracellular calcium. Such effects were not observed in the absence of extracellular calcium. Translocational effects with exposure of MNNG was further enhanced in the presence of hydrocortisone. The result suggests that the type of PKC involved may be $Ca^{2+}$-dependent classical isoform and steroid hormone enhances PKC activation. Among cPKC isoforms examined, only $PKC-{\alpha}$ and r showed significant translocation of protein levels from cytosolic fraction to membrane fraction, as analyzed by immunoblot. $PKC-{\varepsilon}$ in nPKC class showed an inch·eased translocation, but other forms in this class did not show the effect. None of isoforms in aPKC class was affected by MNNG treatment. The study demonstrated that there was a certain specificity in the patterns of isoform induction follwong chemical carcinogen exposure and helped identify all the types of PKC isoforms expressed in human epithelial cells. It was revealed that PKC isoforms were activated in an early resonse to chemical carcinogen, suggesting that PKC be associated with carcinogenesis process from an early stage in this particular cell system. The study will contribute to improving our understanding of chemical-induced carcinogenesis in human cells and may provide a scientific basis to introduce the specific PKC inhibitors as an anticancer drug of epithelial cell-origin cancers including oral cancer.