• Genomics & Informatics
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• v.2 no.2
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• pp.75-80
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• 2004

In a variety of animal species, the perinatal exposure of experimental animals to the 2,3,7,8-tetrachlorodibenzo­p-dioxin (TCDD) leads to the immune dysfunction, which is more severe and persistent than that caused by adult exposure. We report here the changes of gene expression and the identification of the marker-genes representing the dioxin exposure. The expressions of the transcripts were analyzed using the 11 K oligonucleotide­microarray from the bone marrow cells of male C57BL/6J mice after an intraperitoneal injection of $1{\mu}g$ TCDD/kg body weight at various time intervals: gestational 6.5 day(G6.5), 13.5 day(G13.5), 18.5 day(G18.5), and postnatal 3 (P3W)and 6 week (P6W). The type of self-organizing maps(SOM) representing the specific exposure dioxin could be identified as follows; G6.5D(C14), G13.5D(C0, C5, C10, C18), G18.5D(7): P3W(C2, C21), and P6W(C4, C15, C20). The candidate marker-genes were restricted to the transcripts, which could be consistently expressed greater than $\pm$2-fold in three experiments. The resulting candidates were 85 genes, the characteristics of that were involved in cell physiology and cell functions such as cell proliferation and immune function. We identified the biomarker-genes for dioxin exposure: smc -like 2 from SOM C14 for the dioxin exposure at G6.5D, focal adhesion kinase and 6 other genes from C0, and protein tyrosine phosphatase 4a2 and 3 other genes from C5 for G13.5D, platelet factor 4 from C7 for G18.5D, fos from C2 for P3W.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.145-145
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• 2002

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a prototype and the most potent chemical of the polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (dioxins). A variety of studies on the toxic effects of dioxin and related compounds have been conducted internationally since 1990.(omitted)

• Environmental Mutagens and Carcinogens
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• v.26 no.3
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• pp.77-85
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• 2006

2,3,7,8-Tetrachlorodibenzo-$\rho$-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 (MARKs) phosphorylation and cyclin D1 overexpression are induced by TCDD, which corresponded with the progression of cellular proliferation. However, TCDD did not affected Ha-ras 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.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.469-476
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• 2012

2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is an environmental toxicant with a polyhalogenated aromatic hydrocarbon structure and is one of the most toxic man-made chemicals. Exposure to 2,3,7,8-TCDD induces reproductive toxicity, immunotoxicity, and hepatotoxicity. In this study, we evaluated how 2,3,7,8-TCDD-induced hepatotoxicity affect the expression of heat shock proteins and antioxidant enzymes using the real-time polymerase chain reaction (PCR) in rat. 2,3,7,8-TCDD increased heat shock protein (Hsp27, ${\alpha}$-B-crystallin, Mortalin, Hsp105, and Hsp90s) and antioxidant enzymes (SOD-3, GST and catalase) expression after a 1 day exposure in livers of rats, whereas heat shock protein (${\alpha}$-B-crystallin, Hsp90, and GRP78) and antioxidant enzymes (SOD-1, SOD-3, catalase, GST, and GPXs) expression decreased on day 2 and then slowly recovered back to control levels on day 8. These results suggest that heat shock proteins and antioxidant enzymes were induced as protective mechanisms against 2,3,7,8-TCDD induced hepatotoxicity, and that prolonged exposure depressed their levels, which recovered to control levels due to reduced 2,3,7,8-TCDD induced hepatotoxicity.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.94-94
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• 2003

Endocrine disrupters (EDs) are exogenous chemicals that interfere with the production, releasing, metabolism, excretion, binding of natural hormones, and whole endocrine systems. EDs are very dangerous since they are extremely stable, not easily degraded, and accumulated in fat and tissue. 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is known as the most toxic EDs. Therefore, this study was conducted to investigate the effects of TCDD on proliferation of human breast cancer (MCF-7) and endometrial adenocarcinoma (Hec-1B) cells. 10, 100, and 1000 nM of TCDD were treated with steroid free condition. Viable cell counting, MTT, and BrdU assay was performed to investigate cell proliferation. Apoptosis was investigated using DNA laddering. Although, DNA fragmentation as the evidence of apoptosis was not detected, all of these cell lines showed restricted proliferation at 48 hrs after 100 and 1000 nM TCDD treatments. Recently, it has been reported that the expression of transforming growth factor $\beta$s (TGF-$\beta$s) are increased in TCDD treatment and also involved in regulation of cell cycle. Therefore, these results were considered that the decreased cell prolifcration by TCDD is related to the expression of TGF-$\beta$s.

• Environmental Engineering Research
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• v.11 no.5
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• pp.241-249
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• 2006

A mathematical model is described for the prediction of convective upward transport of an organic solvent driven by evaporation at the surface, which is known as the major transport mechanism in the in-situ photolysis of a soil contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD). A finite-element model was proposed to incorporate the effects of multiphase flow on the distribution of each fluid, gravity as a driving force, and the use of hysteretic models for more accurate description of k-S-p relations. Extensive numerical calculations were performed to study fluid flow through three types of soils under different water table conditions. Predictions of relative permeability-saturation-pressure (k-S-p) relations and fluids distribution for an illustrative soil indicate that hysteresis effects may be quite substantial. This result emphasizes the need to use hysteretic models in performing flow simulations including reversals of flow paths. Results of additional calculations accounting for hysteresis on the one-dimensional unsaturated soil columns show that gravity affects significantly on the flow of each fluid during gravity drainage, solvent injection, and evaporation, especially for highly permeable soils. The rate and duration of solvent injection also have a profound influence on the fluid saturation profile and the amount of evaporated solvent. Key factors influencing water drainage and solvent evaporation in soils also include hydraulic conductivity and water table configuration.

• YAKHAK HOEJI
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• v.50 no.4
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• pp.220-227
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• 2006

The therapeutic effect of tissue cultured root of mountain ginseng (Panax ginseng) (tcMG) on 2,3,7,8-tetrachlorodaibenzo-p-dioxin (TCDD) induced toxicity in rat was investigated. The rats were assigned into three groups (10 rats/group), control, TCDD exposed group and tcMG treated group after TCDD exposed. $50\;{\mu}g/kg$ of TCDD was injected by i.p. for TCDD exposed group and 30 mg/kg of tcMG saponin was administered for 4 weeks by oral gavage for tcMG treated group. The weights of body, spleen, kidney, thymus, testes and epididymides were decreased in the single TCDD treatment. However these organs was significantly recovered by tcMG saponin except thymus (p<0.05). tcMG decreased the level of hepatic demage maker enzymes, AST and ALP. It also lowered total cholesterol and triglyceride. The level of serum triglyceride was significantly decreased in tcMG saponin treated group compared with the control. Histopathological examination revealed morphological change in the liver spleen, thymus and testes of TCDD treated rats. However they were relatively well preserved in the tcMG treatment group. In conclusion, TCDD induced toxicity was some repaired by tcMG. tcMG may be useful for prevention and treatment of TCDD induced toxicity.

• Natural Product Sciences
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• v.14 no.2
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• pp.73-80
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• 2008

The authors screened the pharmacological effects of 50% ethanol extracts of Yacon on spermatogenesis in rats. Numbers of sperm in animals treated with 25, 50, or 100 mg/kg/day for 6 weeks of Yacon tuber extracts (YTE) were approximately 1.51, 1.61 and 1.78 times higher, respectively, than in the untreated control group. Moreover, the spermatogenic effect of Yacon leaf extract was found to be $1.03{\sim}1.38$ times higher than that of YTE. The ameliorative effect of Yacon tuber extracts on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced toxicities in the rat were also investigated. Rats were assigned to three groups (6 rats/group), a control group, a TCDD exposed group, and a group treated with Yacon tuber extract (YTE) after TCDD exposure (TCDD/YTE group). 40 ${\mu}g/kg$ of TCDD was injected i.p., and 200 mg/kg/day of YTE was also administered for 4 weeks by oral gavage. The TCDD/YTE group showed a significant increase in sperm number as compared with the TCDD exposed group. In conclusion, TCDD induced testicular toxicity was significantly ameliorated by YTE. The results of the present study suggest that Yacon extract is a possible therapeutic for the treatment of spermatogenic disorder.

• Journal of Preventive Medicine and Public Health
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• v.34 no.1
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• pp.80-88
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• 2001

Objectives : In an epidemiologic study on the health impact of Agent Orange exposure, the valid estimation of exposure level is the most important step. Based on recent studies, we examined the correlation between exposure levels categorized by personal exposure estimates and serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD, Dioxin), exploring the possibility of utilizing the exposure level as a surrogate for the estimate of exposure to agent orange. Methods : During the study period (Jan 1996-Feb 1996), blood specimens of 745 subjects taken randomly among 1,329 persons and kept frozen, were analyzed for 2,3,7,8-TCDO and six other dioxin congeners. The serum dioxin and congeners were measured in 1998 by CDC, adjusted for serum lipids. We categorized the total exposure scores into five groups based on Agent Orange exposure data collected by interview and military records. Pearson and Spearman's correlation coefficients & multiple regression analysis were used to identify the relationship of the exposure level categorized with serum concentration of 2,3,7,8-TCDD, and six other dioxin congeners. Results : Dioxin and the other congeners, except 1,2,4,6,7,8-HpCDD, showed significant correlations to exposure categories (p<0.005): 2,3,7,8-TCDD and OCDD showed positive correlations, whereas the other congeners did negative. The values of 2,3,7,8-TCDD differed according to exposure category and proportionally increased from the low exposure group to the high, a dose-response relationship, even after other possible confounding variables were adjusted for. In multiple regression analysis, age$(\beta=0.033)$, dioxin$(\beta=0.433)$, 1,2,3,7,8-PeCDD$(\beta=-0.998)$, 1,2,3,4,7,8-HxCDD$(\beta=-0.773)$, 1,2,3,6,7,8-HxCDD$(\beta=0.255)$, 1,2,3,7,8,9-HxCDD$(\beta=-3.468)$, 1,2,3,4,6,7,8-HpCDD$(\beta=0.109)$ we re found to be significantly related to the total exposure score(p<0.005). Conclusion : This study demonstrated that the use of such categorizations as a surrogate measure of agent orange exposure in identifying exposure degrees in a health impact study is valid.

• Environmental Mutagens and Carcinogens
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• v.24 no.2
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• pp.91-98
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• 2004

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) is a powerful carcinogen in several species, limited model system exist to study carcinogenicity of this compound at cellular level. To enhance our under-standing of carcinogenicity of TCDD at cellular level, we investigated micronucleus (MN) frequency as a index of genetic toxicity and whether TCDD can transform the human cells in culture. Normal human cell lines, skin keratinocyte HaCaT, Chang liver and breast MCF10A cells were used. TCDD did not affect the cell viability of the Chang liver, HaCaT and MCF10A cells. The frequency of micronucleus was increased after treatment of TCDD for 24hr in Chang liver and HaCaT cells, but not changed in MCF10A cells. And we observed putative transformed cells in Chang liver cells exposed to 1 $\mu$M TCDD for 2 weeks. The putative transformed cells were also observed in HaCaT cells with subsequent exposure to TCDD (0.1, 1, 10, 100 nM) for 2 weeks after initial exposure to MNNG, but not observed in MCF10A cells. Collectively, these results indicate that the ability of TCDD to induce micronuclei may be involved in cellular transformation of Chang liver and HaCaT cells. Our putative TCDD-transformed cells of Chang liver and HaCaT are expected to provide a clue to the elucidation of TCDD-induced transformation pathway.