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KMID : 0382320060260030077
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Environmental Mutagens and Carcinogens
2006 Volume.26 No. 3 p.77 ~ p.85
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Tumorigenic Effects of 2,3,7,8-tetrachlorodibenzo-ρ-dioxin in Normal Human Skin and Lung Fibroblasts
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Kang Mi-Kyung
Kim Ok-Hee
Kim Kang-Ryune
Kang Ho-Il
Ryeom Tai-Kyung
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Abstract
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2,3,7,8-Tetrachlorodibenzo-ρ-dioxin (TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although TCDD is recognized as potent carcinogens, relatively little is known about their role in the tumor promotion and carcinogenesis. It is known that TCDD can increase of cancer risk from various types of tissue by a mechanism possibly involving the aryl hydrocarbon receptor (AhR) activation. In this study, effects of TCDD on cellular proliferation of normal human skin and lung fibroblasts, Detroit551 and WI38 cells were investigated. In addition, to enhance our understanding of TCDD-mediated carcinogenesis, we have investigated process in which expression of Erk1/2, cyclinD1, oncogene such as Ha-ras and c-myc, and their cognate signaling pathway. TCDD that are potent activators of AhR-mediated activity was found to induce significant increase of cytochrome P4501A1 mRNA expression, suggesting a presence of functional AhR. These results support that CYP1A1 enzyme may be involved in the generation of TCDD-induced toxicity. Moreover mitogen-activated protein kinases (MAPKs) phosphorylation and cyclin D1 overexpression are induced by TCDD, which corresponded with the progression of cellular proliferation. However, TCDD did not affected Haras and c-myc mRNA expression. Taken together, it seems that TCDD are could be a part of cellular proliferation in non-tumorigenic normal human cells such as Detroit551 and WI38 cells through the upregulation of MAPKs signaling pathway regulating growth of cell population. Therefore, AhR-activating TCDD could potentially contribute to tumor promotion and Detroit551 and WI38 cells have been used as a detection system of tumorigenic effects of TCDD.
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KEYWORD
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2,3,7,8-tetrachlorodibenzo-ρ-dioxin, aryl hydrocarbon receptor, cytochrom P4501A1, Detroit551, WI38, mitogen-activated protein kinases
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