• Toxicological Research
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• v.25 no.1
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• pp.35-40
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• 2009

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and related halogenated aromatic hydrocarbons elicit a diverse spectrum of biochemical and toxic responses in laboratory animals and mammalian cells in culture. Toxicity and carcinogenicity of TCDD is well established but the molecular mechanism is still poorly understood. Here, we found the noble responsive genes to TCDD using the differential display analysis. Treatment of HepG2 cells with TCDD showed a significantly different mRNA expression pattern from the untreated cells in differential display analysis. The differentially displayed bands were isolated and used as probes in dot blot and Northern blot analyses. Of thirty-five isolated differentially displayed bands, only two bands were confirmed as positive in dot blot and Northern blot analyses. The nucleotides sequences of these clones were analyzed and the search of Genebank database revealed that one clone is highly homologous with RanBP2 (Ras-related nuclear protein binding protein2; 92%) and the other is an unknown gene. RanBP2 is a nucleoporin with SUMO E3 ligase activity that functions in both nucleocytoplasmic transport and mitosis and its role as a novel tumor suppressor has been recently proposed. Thus, these results may suggest the clue elucidating the toxic mechanism of TCDD through RanBP2.

• Proceedings of the Korean Society of Toxicology Conference
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• 2005.05a
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• pp.176-176
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• 2005

• Journal of Preventive Medicine and Public Health
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• v.36 no.4
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• pp.303-313
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• 2003

General information is summarized, that is necessary to introduce a scientific assessment of the human health and exposure issue concerning dioxin and dioxin-like compound. Scientific literatures were reviewed to assess the background exposures to the dioxin-like compounds for normal residents. Epidemiologic studies were also reviewed to assess malignant and nonmalignant sweets of dioxins. In 1997, the International Agency for Research on Cancer classified 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a human carcinogen, primarily based on occupational cohort studies. The US Environmental Protection Agency made the same decision in it's Draft Dioxin Reassessment. Epidemiologic evidences point to a generalized excess of all cancers, without any pronounced excess at specific sites. Reported non-cancer effects included a range of conditions affecting most systems. Among them, chloracne, elevation in gamma glutamyl transferase(GGT), and alterations in reproductive hormones are related to TCDO, Other adverse outcomes, such as lipid concentrations, diabetes, circulatory and heart diseases, immunologic disorders, neurobehavioral effects, and developmental outcomes require further study before their respective relationships to TCDD can be more definitively assessed.

• Journal of Life Science
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• v.11 no.4
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• pp.346-353
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• 2001

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) a prototype of the highly toxid halogenated arylhydrocarbons, bioaccumulates in the food chain and induces a complex spectrum of pathological responses. However, its effect on the nerve system is relatively not well studied. In this study we evaluated TCDDs cytotoxicity on the cortical cell and investigated its effect on the expression 2,3-cyclic nucleotide 3-phosphodiesterase(CNPase), a marker for oilgodendrocytes, The survival rates of 4 DIV cortical cells, that are dissociated from E18 rat cortex and maintained in the presence of TCDD, were 88.8, 83.6, 78.5, and 78.6%(5,10, 20 and 50 nM, respectively) where the reduction in 20 and 50mM TCDD were statistically very significant(p<0.01). Imunocytochemistry of cultured cells revealed that the intensities of immunostaining with an anti-CNP1&2 antibody depended on the concentrations of the toxin. Immunoblot analysis also showed differential expression of CNP1 and CNP2 in the presence of TCDD; the CNP1 expression was dose-dependently decreased. Interestingly, the expression of CNP2 in the presence if TDCC; the CNP1 expression was dose-dependently decreased. Interestingly, the expression of CNP2 fluctuated with the TCDD concentration. These results indicated that CNP1 and 2 are differentially regulated by TCDD, implying the functions of oligodendrocytes are modulated by the toxin.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4809-4813
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• 2014

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

• Journal of Digital Convergence
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• v.11 no.4
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• pp.339-350
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• 2013

The decreased body, liver, kidney, spleen and testis weights of guinea pigs by TCDD (2,3,7,8-tetracholorodibenzo-${\rho}$-dioxin) treatment (TT) were statistically significantly increased after treating red ginseng saponin fraction (SF) (p>0.01). After treated with SF, the decreased hematocrits values and numbers of RBC and platelet, activity of amylase and lactate dehydrogenase, levels of uric acid, total protein and albumin by TT were increased, and the increased numbers of WBC, levels of triglyceride, total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, creatinine, blood urea nitrogen, calcium and phosphorus, activities of creatinine kinase, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were decreased after treated with SF. And they all had a statistical significance (p>0.01) except for RBC, WBC, platelet, blood glucose, TC, calcium and albumin. From these results, we knew that SF mollified the acute toxicity induced by TCDD in guinea pigs.

• Korean Journal of Environmental Biology
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• v.21 no.2
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• pp.170-176
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• 2003

The effect of xenobiotics on cytochrome P450 (CYP) and 7-ethoxyresorufin-O-deethylase (EROD) in hepatopancreatic microsome of surf clam, Coelomactra anti-quata, were investigated. The microsome isolated from the digestive gland of the surf clam, collected from the east coast of Korea, was in vitro exposed to p, p -DDT (0.1,0.4 and 1.0 mM) for 30 min and 2,3,7,8-TCDD (0.01, 0.04 and 0.1 ppb) and PCB-153 (0.01, 0.04 and 0.1 ppb) for 7 hr. In the case of DDT exposure, the CYP content and EROD activity of 1.0 mM exposure group increased up to about 117% and 120% of the DMSO solvent control group after 10 min. exposure, respectively. After 2 hr exposure of TCDD, the CYP content and EROD activity were also induced to the range of 103∼110% and 121∼139%, respectively. The PCB-153 exposure group showed 107∼115% of CYP content and 129∼140% of EROD activity after 2 hr exposure. Three test chemicals apparently induced CYP and EROD activity in the microsome of surf clam. The inducing potentials depend en the test chemicals.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5117-5121
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• 2014

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells were used as a tumorigenic model. These were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. Expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, were subsequently down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD and various concentrations of LRE showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analyses also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated disease.

• Environmental Mutagens and Carcinogens
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• v.24 no.4
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• pp.155-162
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• 2004

In mammalian, cytochrome P4501A1 (CYP1A1) is very important for metabolism of xenobiotics such as PAHs(Polycyclic aromatic hydrocarbon) and heterocyclic amine, and it is induced by environmental contaminants such as PAHs, TCDD(2,3,7,8-tetrchlorodibenzo-p-dioxin) and 3-MC (3-methylcholanthrene). In fish, like mammalian, when it is exposed to environmental contaminants, they cause specific and sensitive induction of CYP1A. Therefore, induction of CYP1A in fish and mammalian is widely used as a biomarker for exposure of environmental contaminants. In this study, to compare the function of Cyp1a1 in fish with it in mammalian, we have used rainbow trout(Oncorhynchys mykiss) hepatoma cells (RTH-149) and mouse hepatocyte (Hepa-I). in order to examine induction of Cyp1a1 by TCDD, we have used the bioassay system. We examined effects of TCDD on the Cyp1a1-luciferase reporter gene activity, 7-ethoxyresorufin O-deethylase(EROD) activity and Cypa mRNA level.

• Environmental Analysis Health and Toxicology
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• v.17 no.3
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• pp.225-238
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• 2002

유해물질의 거동에 대한 이해를 돕기 위해서 대도시지역을 대상으로 하여 fugacity를 이용한 level-III 다매체환경거동모형이 개발되었다. 이 모형에 의한 거동의 예측결과에 민감한 영향을 주는 입력과정과 변수들을 찾아내기 위하여 체계적으로 민감도분석을 수행할 수 있도록 하는 기법을 개발하고 사례연구로서 서울지역과 2, 3, 7, 8-TCDD을 대상으로 그 기법을 적용하였다. Sensitivity index에 의한 평가한 결과, 일정한 배출속도조건에서는 대기중의 바람속도, 그리고 대기에서 수체나 토양으로 전이되는 건식 및 습식 침적과정이 다매체거동에서 전체적으로 가장 중요한 과정인 것으로 나타났다. 또한 이들 거동과정 자체에 영향을 미치는 변수들에 대한 민감도 분석의 결과 건식침적의 경우 중력에 의한 입자들의 침강속도가, 습식침적의 경우 평균 강우속도가 대단히 중요한 변수임이 파악되었다. 물질의 물리화학적 특성 가운데에서는 z-값에 직접 영향을 주는 변수들, 즉, 헨리상수와 옥타놀-물 분배계수 등이 결과에 민감한 영향을 주는 것으로 나타났다. 이러한 사례연구는 본 연구에서 개발된 민감도분석기법이 유해물질의 다매체 거동모형을 개선하고 좀더 중요한 거동과정에 대한 이해를 넓히는데 효율적으로 사용될 수 있다는 것을 보여주고 있다.