• BMB Reports
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• v.32 no.3
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• pp.279-287
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• 1999

The aromatic hydrocarbon receptor (AhR) is a cytosolic protein that binds the environmental pollutant, dioxin. The liganded AhR translocates into the nucleus where it heterimerizes with a constitutive nuclear protein, AhR nuclear translocator (Arnt). The N-terminal regions of both AhR and Arnt contain basic helix-loop-helix (bHLH) and Per-AhR-Arnt-Sim (PAS) motifs that are required for DNA binding, dimerization, and ligand binding whereas the C-terminal regions of both AhR and Arnt contain transactivation domains. Here, results from the mammalian two-hybrid system indicate that Arnt can make a homodimer but AhR cannot. In the presence of dioxin, the interaction between AhR and Arnt is stronger than that of the Arnt homodimer, suggesting that Arnt prefers to make a heterodimer with the liganded AhR rather than a homodimer. Transfection analyses using the GAL4-driven reporter system suggest that AhR's N-terminal region represses its own transactivation domain, as well as exogenous transactivation domains such as Sp 1 and VP16. Interestingly, the repressed transactivation domains of AhR are activated by ligand-dependent heterodimerization with Arnt. These observations suggest that heterodimerzation with Arnt is necessary not only for DNA binding but also for activation of the repressed transactivation capability of AhR.

• Journal of Environmental Health Sciences
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• v.26 no.3
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• pp.11-17
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• 2000

There are among the most relevant toxic emissions from incinerators such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (PCBs). Induction of cytochrome P4501A1 catalyzed 7-ethoxyresorufin O-deethylase(EROD) activity in mammalian cell culture(EROD bioassay) is thought to be a selective and sensitive parameter used for the quantification of dioxin-like components. In this study, the toxic emissions from several school waste incinerators were evaluated by determination of CYPIA catalytic activity and cytotoxicity using cell culture microbioassay. The incinerator residue and soil samples were collected from the schools located in Kyunggi province from April to June 1999. The samples were extracted in a Soxhlet apparatus using toluene for 20 hours. In order to clean-up, concentrated crude extracts were applied to basic alumina column. The EROD activities of extracts in the H4IIE cells were from 1.91$\pm$0.32 ng-TEQ/g to 24.54$\pm$3.48 ng-TEQ/g of biochemical-TEQ value. In soil samples, CYP1A catalytic activity was 0.09~0.64 ng-TEQ/g. EROD bioassay, seems to be a useful short-term bioassay when information about the biological response of complex environmental samples is needed. Although further study is needed, these results indicate that the potent toxic emissions are produced from school waste semi-incinerators.

• Environmental Mutagens and Carcinogens
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• v.22 no.4
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• pp.312-318
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• 2002

Dioxin represents a group of halogenated aromatic hydrocarbons of which 2,3,7,8-tetrachlorod-ibenzo-p-dioxin (TCDD) is well known for its extremely toxic properties as well as ubiquitous presence in our environment and ecosystems. In order to better assess the carcinogenic mechanism of dioxin, we should utilize the reliable biomarkers that can precisely and correctly reflect multi-stage carcinogenesis. When MCF10A cells were exposed to TCDD (10 nM), expression of both CYP1A1 and CYP1B1 was induced in a time-related manner. The expression as well as activity of ornithine decarboxylase was transiently induced by TCDD treatment. In contrast, the induction of COX-2 that is implicated in carcinogenesis as well as inflammation, was not induced by TCDD. In another study, gap-junctional intercellular communication (GJIC) was attenuated by TCDD treatment as revealed by the dye-transfer assay. Based on these findings, TCDD has both tumor initiating and promoting potential in human breast epithelial cells in culture. Also, treatment of MCF10A cells with the carcinogen 7,12-dimethylbenz[a]anthracene plus TCDD resulted in malignant cell transformation as revealed by increased anchorage-independent growth of exposed cells. Additional studies may be necessary to assess the effects of TCDD on multi-stage carcinogenesis in vivo.

• Toxicological Research
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• v.17
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• pp.25-35
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• 2001

In 1990, Tolerable Daily Intake (TDI) of 10 pg TCDD/kg/day for dioxins based on carcinogenicity and reproductive toxicity was determined by WHO/EURO, that resulted in the establishment of TDIs in other countries. In Japan, Ministry of Health and Welfare and Environment Agency, respectively established the TDI of 10 pg TCDD/kg/day and Health Risk Assessment Index of 5 pg TCDD/kg/day in 1996. Accumulation of new scientific data, especially by molecular toxicology since 1990, resulted in the reevaluation of TDI by WHO-ECEH and IPCS in May, 1998. At this meeting, it was stressed that \circled1 toxic effects of dioxin is mediated through Ah-receptor in both animals and humans, \circled2 use of ebody burdeni concept is better than the use of traditional NOAEL/UF approach, \circled3 inclusion of coplanar PCBs in the TDI by the use of new WHO-TEF. LOAELs (0.16~200 ng TCDD/kg/day) obtained from reproductive toxicity and immunotoxicity in rats, and neurobehavioral toxicity and induction of endometriosis in rhesus monkeys are calculated to be the body burden of 10~50 ng TCDD/kg that is 14~37 pg TEQ/kg/day as human daily intake. Finally TDI of 1~4 pg TEQ/kg/day was established by applying the UF of 10. In Japan, reproductive toxicity and immunotoxicity in rats were used to obtain LOAELs (100~200 ng TCDD/kg/day). Finally TDI of 4 pg TEQ/kg/day was established in June 1999 by applying the UF of 10 to human daily intake of 43.6 pg TEQ/kg/day which corresponds to the body burden of 86 ng TCDD/kg.

• Journal of Korean Society for Atmospheric Environment
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• v.19 no.5
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• pp.469-490
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• 2003

Atmospheric concentrations of persistent organic pollutants (POPs) were measured at Gosan, Jeju in November 2001 and spring 2002, each time for two weeks. Primary target pollutants were organochlorine pesticides, coplanar polychlorinated biphenyls (co- PCBs), and dioxin/furans listed in the Stockholm Convention adopted in May 2001. Polycyclic aromatic hydrocarbons (PAHs) were also measured in order to understand the overall characteristics of the POPs distribution as well as PM$_{2.5}$, a potent carrier of POPs. In the latter part of the measurement period of November 2001, almost every pollutant of combustion origin including dioxin/furans went high probably due to influence of emissions in the nearby area. The characteristics of atmospheric environment at Gosan in this period were rather close to urban areas far from those of a background area. A severe dust storm swept for three days at the end of the measurement period of spring 2002. However, changes in pollutant concentrations were relatively small except PM$_{10}$. Nevertheless, increases in particulate PAHs and OCDD (octachlorinated dibenzo-p-dioxins), mostly present in fine particles, were observed. Trends in organochlorine pesticide variations were mixed although possible volatilization of DDT residues from soil was inferred from the measurements of spring 2002.2.2.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.88-92
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• 2009

The effect of Chlorella vulgaris (CV) on the urinary excretion of di-ortho PCB congeners (PCB-138, -153) was investigated. Sprague-Dawley rats (6-weeks-old, n=10 rats/group) were randomly divided into one control (0CV) or 2% CV (2CV) or 5% CV (5CV) or 10% CV (10CV) groups, respectively. Composition of normal and chlorella meal-based diet were made up of 30% casein, 15% cornstarch, 50% sucrose, 5% cellulose, 5% coconut oil, 3.5% mineral mixture, 1 % vitamin mixture. All rats had free access to water and diet for 4 weeks. A significant increase in both PCB 138 and 153 in urinary level was detected in CV fed groups, 540% and 167% for 2CV, 155% and 89% for 5CV, 114% and 144% for 10CV group, respectively, when compared with their controls. These findings suggest that CV may have potential to eliminate body burden levels of dioxin-like PCB compounds.

• Journal of Environmental Health Sciences
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• v.35 no.4
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• pp.259-268
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• 2009

This study was carried out to investigate the protective effect of Red Ginseng Saponins on 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced toxicities in guinea pigs ($200{\pm}10$ g). Normal control (NC) group guinea pigs ($200{\pm}10$ g) received vehicle and saline, while the TCDD-treated (TT) group was given water-extract (WE), saponin fraction (SF) and non-saponin fraction (NSF). Korean red ginseng fractions were administered from 1 week before TCDD-exposure for 4 weeks. Body weight loss and deteriorated clinical parameters related to sugar metabolism and liver function such as lipase and AST, respectively, these were significantly reduced by both saponin and non-saponin fractions. However, increase of lipase was attenuated by the saponin fraction in a dose-dependent manner. Only AST was affected by the saponin fraction. The results suggest that saponins are active substances in the Korean red ginseng water extract against TCDD induced toxicities in Guinea pigs.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.166-166
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• 2002

The response of environmental pollutants can be detected bioanalytically focusing on the source and matrices of concern. Cell culture bioassays are rapid and inexpensive, and thus have great potential for determination of environmental pollution. We have examined the estrogenic and dioxin-like activites of industrial wastewater using E-screen assay and EROD microbioassay. Influent and effluent wastewater were collected from four different industrial wastewater treatment plants, such as cosmetics, paints, textile producing and metal coating plant, and extracted using solid-phase extraction with Oasis＠HLB plus cartridge. Pollutants adsorbed to the cartridge were eluted with MTBE. MCF-7 cells were treated with extracts showed various estrogenic potential. The textile wastewater showed strong estrogenic activity and the others showed weak estrogenic activity, No effect was observed in the wastewater from paints producing plant. All extracts showed CYPIA inducing effects, indicating these samples contain dioxin-like chemicals. Bioanalytical results of effluents compared with influents could give us information about the incomplete wastewater treatment and biological potency caused by pollutants. [Supported by a Grant from the Korea Science and Engineering Foundation]

• Environmental Analysis Health and Toxicology
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• v.19 no.1
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• pp.1-24
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• 2004

Since dioxins became a serious concern in Korea, a significant number of investigations have been conducted to address diverse issues related to dioxins. However, the results have not been organized for ready access and use. The principal purposes of the work were to ⅰ) provide an archive of dioxin researches in Korea and ⅱ) give an overview of dioxin contamination. The focus of this work was placed on the contamination levels and characteristics concerning the waste incinerators emissions, environmental media, and biological samples(fishes/shellfishes, foods, and human body). Principal component analysis was conducted to identify common and/or unique features and the important variables associated with the congener patterns. From a comprehensive search of academic journals, research and monitoring project reports, dissertations, and periodicals of other forms, a total of 115 counts were found that met the purposes of this study. The contamination levels of various samples were summarized and compared to those reported in foreign literatures. The congener patterns varied largely with environmental media and distinguished particularly by OCDD, 1,2,3,4,6,7,8-HpCDF, and OCDF for the samples within the same media. The proximity to emission sources differentiated the congener patterns in air and soil samples by the fraction of OCDD.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2002.07a
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• pp.238-238
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• 2002

We studied whether kinase pathways are involved in TCDD-induced gene expression by treating specific kinase inhibitors ncluding MEK1 inhibitor PD98059, p38 inhibitor SB202190, PI-3 kinase inhibitor Wortmannin or LY294002 or protein tyrosine kinase inhibitor Genestein and then tested the effects of individual inhibitors on TCDD-induced gene expression of cytochromelAl gene (CYPlAl). Our results show that PD98059, MEK-1 inhibitor reduces dioxin-inducible transcription of CYPlAl. p44/p42MAPK, that is phosphorylated by Mek-1, are phosphorlylated by treatment of TCDD, peaking at lnM, 30min treatments. Overexpressions of p44/p42 MAPK dominant negative mutants suppress dioxin dependent transcription of DRE-driven reporter gene in a dose-dependent manner. Our results demonstrate that p44/p42 MAPK is essential for transcriptional activity of AHR/ARNT heterodimer. We found that PD98059 dose-dependently blocks TCDD-induced DRE binding of the AHR/ARNT heterodimer, thereby it reduces TCDD-induced gene expression. Therefore, our results indicate that Mek-1/p44/p42 MAPK pathway is involved in TCDD-induced gene expression, [This study was supported by a grant from Korean Research Foundation Grant (X01529)to H. Park]