• The Korean Journal of Physiology and Pharmacology
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• 제10권6호
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• pp.349-354
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• 2006

The aromatic hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the biological and toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related chemicals. The application of recombinant reporter plasmid such as the firefly luciferase gene has proven to be a very effective method to detect these chemicals. The bioassay system, CALUX, is sensitive in directly detecting AhR-agonists from a variety of environmental and biologic materials. However, responses of the AhR-dependent bioassays are dependent on the cell types used. Thus, we developed a sensitive bioassay using the recombinant mouse hepatoma cell (Hepa1c1c7) for the determination of dioxins. The recombinant cell line was stably transfected with firefly luciferase reporter gene (pGudLuc1.1). The transfected cells showed the highest induction of luciferase activity at 4.5 hr and a decrease beyond this time point. The system showed the highest sensitivity of detection ever reported. Upon TCDD exposure cells showed 2 fold increase at 10 pM and 7 fold increase at 100 pM, respectively. The passage number after the transfection played an important role in the sensitivity. The increase of passage number tended to increase the sensitivity of the cells up to 15. The media without phenol red showed a higher induction rate than with phenol red, suggesting the preferable use of phenol red-free media for the bioassay. Since each of the assays has unique characteristics that make them suitable for some screening applications and not others, development of sensitive bioanalytical methods based on a variety of cellular systems in a key to the successful determination of dioxins. The bioassay system developed in this study will contribute to further development of successful screening the AhR agonists among the environmental mixture. In addition, the rapid and sensitive nature of this cellular system can be applied as a valuable tool to screen the dioxin-like moieties among the prodrugs at the initial stage, thereby expediting the new drug discovery.

• 한국지하수토양환경학회지:지하수토양환경
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• 제9권3호
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• pp.20-26
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• 2004

2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)로 오염된 토양의 현장 광분해 정화 과정에서 가장 중요한 이동 메커니즘인 지표에서의 증발 및 광분해에 의한 유기 용매의 이류 상방향 이동에 대한 수식화와 모델 개발을 수행하였다. 각 유체 분포에 대한 다상 유동 효과, 구동력으로서의 중력, k-S-p 관계의 정확한 묘사를 위한 van Genutchen 방정식을 포함한 유한요소법 기반의 수치 모델을 제안하였다. 실험실 규모의 비포화 토양 컬럼 내 용매 이동에 중요한 영향을 미치는 인자들을 조사하기 위하여 수행한 계산의 결과들을 제시하였다. 중력은 고투수성 토양의 유체 분포와 증발에 상당한 영향을 미쳤다. 토양의 종류 또한 증발 과정 중 유체 포화도 분포에 큰 영향을 미친다. 용매의 이류 이동량은 증발량이 증가할수록 초기 물 포화도가 감소할수록 증가하였다. 본 연구에서 수행한 시뮬레이션은 개발된 모델이 토양 환경 내에서 유기 용매의 이류 이동에 영향을 미치는 다양한 인자들의 영향을 분석하는데 유용함을 보여준다.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 추계국제학술대회
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• pp.181-181
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• 2003

We have studied the mechanism of action of TCDD on CYP1A1 promoter activity in both Hepa Ⅰ and MCF-7 cells using transient transfection system with p1A1-Luc reporter gene. When HDAC inhibitors, such as trichostatin A, HC toxin and a novel HDAC inhibitor, IN2001 were cotreated with TCDD to the cells transfected with plAt-Luc reporter gene, the basal promoter activity of CYP1A1 was increased by HBAC inhibitors. Also, in MCF-7 human breast cancer cells, HDAC inhibitors, such as IN2001 and trichostatin A increased the basal activity of CYP1A1 promoter but TCDD stimulated CYP1A1 promoter activity was not changed by HDAC inhibitors. And, in stably-transfected Hepa Ⅰ cells with p1A1-Luc, HDAC inhibitors increased the basal promoter activity only Also, we have investigated the effects of HDAC inhibitors on the human breast and prostate cancer cells in terms of cell proliferation and apoptosis based on SRB assay. IN2001 as well as trichostatin A inhibited the MCF-7, MDA-MB-231, MDA-MB-468, T47D, ZR75-1, PC3 cell growth dose-dependently. The growth inhibition of these cells with HDAC inhibitors was associated with profound morphological change, which suggests the HDAC inhibitors induced apoptosis of cells. The result of cell cycle analysis after 24h exposure of IN2001 showed G2/M cell cycle arrest in MCF-7 cells and apoptosis in T47D and MDA-MB-231 cells.

• Korean Chemical Engineering Research
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• 제47권6호
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• pp.747-754
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• 2009

본 연구에서는 $1,000^{\circ}C$에서 24시간 열처리된 활성탄에서 다이옥신과 유사구조를 갖는 o-DCB(ortho-dichlorobenzene)의 등온흡착식을 실험을 통하여 구하였고, 분자모사를 통하여 예측하였다. 실험으로 분석된 활성탄의 분자식 및 작용기 비율을 바탕으로 초기 활성탄 기본구조를 설계한 후, COMPASS(condensed-phase optimized molecular potentials for atomistic simulation studies) force field를 이용하여 이 구조를 최적화하였다. 최적화된 활성탄 분자구조에서 공극률, 비표면적, 및 입자밀도의 모사결과는 실험값과 비교되었고, 이들에 대한 실험과 모사결과의 오차는 각각 7.62, 3.79, 2.80%를 보여주었다. 통계 열역학적 방법인 GCMC(Grand Canonical Monte Carlo) 기법을 이용하여, 최적화된 활성탄 구조에서 온도에 따른 o-DCB의 등온흡착 상수값을 예측하였으며, 이 모사결과는 실험값과 비교될 때, 3% 이하의 오차를 보였다. o-DCB의 흡착특성을 바탕으로 확인되어진 활성탄 구조에서 다이옥신의 일종인 2,3,7,8-TCDD(tetrachlorodibenzo-p-dioxin) 등온흡착상수, 흡착열, 그리고 기공확산계수를 최종적으로 구함으로서, 실험적으로 구하기 힘든 맹독성 잔류성 유기물질의 흡착특성을 분자모사기법을 통하여 예측하였다.

• 한국산업보건학회지
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• 제26권3호
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• pp.277-285
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• 2016

Objectives: This study was performed in order to evaluate whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could be detected among residents living near Camp Caroll in Waegwan and whether serum concentrations of dioxins, including 2,3,7,8-TCDD, and organochlorine pesticides (OCPs) are associated with length of residence. Methods: Study subjects totaled 113 (for dioxins) and 190 (for OCPs) adults who were selected from participants in a medical investigation. Serum concentrations of dioxins and OCPs were measured using HRGC/HRMS. Information on length of residence was obtained through questionnaires. Results: 2,3,7,8-TCDD was not detected in serum among all subjects. When length of residence was classified as a categorical variable, after adjusting for confounding variables, only residents living in Waegwan for 40 years or longer tended to have high total TEQ values and 2,3,4,7,8-PeCDF with marginal significances. There was no dose-response relation between length of residence and serum concentrations of these chemicals. In multiple regression models with continuous values of the length of residence, total TEQ value and 1,2,3,4,6,7,8-HpCDF were positively associated with length of residence. However, they explained about 3-5% of total variations of serum concentrations of these compounds, while age, consumption of fatty fish, body mass index, alcohol drinking, and cigarette smoking were main variables affecting serum concentrations of dioxins or OCPs. Conclusions: In the current study, high concentrations of certain compounds were mainly observed among persons who lived in Waegwan for at least for 40 years without a dose-response relation. Therefore, it seems difficult to conclude that length of residence meaningfully contributed to the current serum concentrations of dioxins or OCPs among residents in Waegwan. However, considering the half-life of 2,3,7,8-TCDD and indirect exposure routes, the limitations of the current study design should be considered in the interpretation of the study findings.

• Journal of Preventive Medicine and Public Health
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• 제34권1호
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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.

• Tuberculosis and Respiratory Diseases
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• 제78권2호
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• pp.99-105
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• 2015

Background: Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, binds to a wide variety of synthetic and naturally occurring compounds. AhR is involved in the regulation of inflammatory response during acute and chronic respiratory diseases. We investigated whether nuclear receptor coactivator 7 (NCOA7) could regulate transcriptional levels of AhR target genes and inflammatory cytokines in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated human bronchial epithelial cells. This study was based on our previous study that NCOA7 was differentially expressed between normal and chronic obstructive pulmonary disease lung tissues. Methods: BEAS-2B and A549 cells grown under serum-free conditions were treated with or without TCDD (0.15 nM and 6.5 nM) for 24 hours after transfection of pCMV-NCOA7 isoform 4. Expression levels of cytochrome P4501A1 (CYP1A1), IL-6, and IL-8 were measured by quantitative real-time polymerase chain reaction. Results: The transcriptional activities of CYP1A1 and inflammatory cytokines were strongly induced by TCDD treatment in both BEAS-2B and A549 cell lines. The NCOA7 isoform 4 oppositely regulated the transcriptional activities of CYP1A1 and inflammatory cytokines between BEAS-2B and A549 cell lines. Conclusion: Our results suggest that NCOA7 could act as a regulator in the TCDD-AhR signaling pathway with dual roles in normal and abnormal physiological conditions.

• 한국환경생물학회:학술대회논문집
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• 한국환경생물학회 2001년도 학술대회
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• pp.115-116
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• 2001

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.152-152
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• 2002

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.149-150
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• 2002