• Biomolecules & Therapeutics
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• 제8권2호
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• pp.147-152
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• 2000

The rodent uterotrophic assay is currently recommended as one of the primary in vivo assays far endocrine disrupting chemicals by the Organization for Economic Cooperation and Development (OECD) and Endocrine Disruptor Screening and Testing Advisory Committee (US EPA EDSTAC). Generally, this assay relies on the rapid increase in uterus and vagina weights when exposed to estrogenic compounds. Phthalate esters have been used extensively as a plasticizer in the manufacture of plastic products such as PVC films and medical devices. Recently, phthalate esters have been shown to induce endocrine system mediated responses. However, a flew studies have been conducted for the screening of their estrogenic activity. In this study the estrogenic activity of seven phthalate esters, butyl benzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), di-n-butylphthalate (DBP), diethylphthalate (DEP), di-n-pentylphthalate (DPF), di-n-propylphthalate (DPrP) and dicyclohexylphthalate (DCHP), was examined in uterotrophic assay. Phthalate esters dissolved in corn oil were administered to ovariectomized (OVX) female Sprague-Dawley rats by sub-cutaneous injection for three consecutive days. fiats were sacrificed 24h after final treatment, and then uterus and vagina weights were deter mined. All phthalate esters tested in this assay did not change talc uterus and vagina weights at dosage levels up to 200 mg/kg/day treatment. These results demonstrated that phthalate esters did not exhibit estrogenic activity in vivo uterotrophic assay.

• 한국환경생물학회:학술대회논문집
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• 한국환경생물학회 2003년도 학술대회
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• pp.7-11
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• 2003

Interactions of both feminizing and masculinizing chemicals inducing imposex in gastropod were investigated with a long-term exposure experiment. Imposex-free rock shell(Thais-clavigera)was exposed to TBT and other antagonistic chemicals (nonylphenol and DDT), P450 inducer (phenobarbital) and natural sex hormone (estrogen) mixtures for 60 days. None of imposexed-females were found in control, sham (ethanol) and testosterone exposure group, on the other hand imposex was induced in the TBT and all the TBT+antagonist mixture groups. After 60-day exposure, frequency of imposexed-female ranged from 31-68%. Female mean penis length (FMPL) of imposexed-female ranged from 0.87-2.58 mm, and relative penis length indices were from 7.2 to 21.2%. However, the degrees of imposex were different among the exposure groups. The FMPLS of three exposure groups (TBT+estrogen, + DDT and +nonylphe- not) were less than that of the TBT exposure group. Ethoxyresorufin-O-deethylase (EROD) activities in gastropod decreased in the TBT and all the TBT+antagonist ekposure groups compared to the control group. A negative correlation was abtained between TBT body residue and EROD activity, while a positive relationship was obtained between 737 body residue and the degree of imposex except for the TBT +DDT exposure group. Although 737 concentration was relatively high in the TBT+DDT exposure group, the TBT +DDT exposure group demonstrated low EROD activity and low degree of imposex. These results indicate that a certain antagonistic effect of DDT occurred in induction of imposex by TBT.

• 환경생물
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• 제20권2호
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• pp.158-164
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• 2002

합성화학물질의 몇몇은 고등동물의 내분비계를 교란하는 물질로 작용하는 것이 알려져 있다. 다이옥신, 디디티, 피시비 및 비스페놀 에이 등이 내분비계 장애물질로 분류되어 선진 각국에서는 엄격한 통제하에 관리되고 있다. 본 연구는 자주달개비 미세핵 분석법을 이용하여 염색체이상 유발에 있어서의 BPA와 방사선의 상대적 효과를 비교하기 위하여 시행되었다. 홉수처리를 위하여 자주달개비 4430클론의 절취화서를 각각의 농도로 조제된 BPA용액에 여섯시간 동안 침지하고 폭기를 실시하였다. 한편 방사선의 영향을 평가하기 위하여 동일 식물체의 화서군을 양액에 침지한 상태로 0-0.5 Gy까지 선량별로 조사하였다. 실험선량의 범위에서 미세핵 생성률은 분명한 선량-반응 관계를 나타내었으며 BPA 실험농도 범위에 대해서도 농도-반응 관계를 나타내었다. 이들 두 가지 반응 관계식을 이용하여 동일한 미세핵 빈도를 유발하는 방사선량과 비스페놀 에이 농도를 산출할 수가 있는데, BPA $ll.8\mu{M}$은 방사선 피폭 후 임상증상이 나타나기 시작하는 선량인 0.25 Gy에 상응하는 염색체 이상을 유발하는 것으로 확인되었다 본 연구의 결과를 통하여 자주달개비 화분모세포는 비스페놀 에이, 옥틸페놀 또는 노닐페놀 등의 내분비계 장애물질의 생물학적 독성을 평가하는데 유용하게 활용할 수 있는 생물말단 점이라는 것이 입증되었다.

• 상하수도학회지
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• 제28권2호
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• pp.235-248
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• 2014

The widespread occurrence of dissolved endocrine disrupting compounds(EDCs) and pharmaceutical active compounds(PhACs) in water sources is of concern due to their adverse effects. To remove these chemicals, adsorption of EDCs/PhACs on granular activated carbon(GAC) was investigated, and bisphenol A, carbamazepine, diclofenac, ibuprofen, and sulfamethoxazole were selected as commonly occurring EDCs/PhACs in the aquatic environment. Various adsorption isotherms were applied to evaluate compatability with each adsorption in the condition of single-solute. Removal difference between individual and competitive adsorption were investigated from the physicochemical properties of each adsorbate. Hydrophobicity interaction was the main adsorption mechanism in the single-solute adsorption with order of maximum adsorption capacity as bisphenol A > carbamazepine > sulfamethoxazole > diclofenac > ibuprofen, while both hydrophobicity and molecular size play significant roles in competitive adsorption. Adsorption kinetic was also controled by hydrophobicity of each adsorbate resulting in higher hydrophobicity allowed faster adsorption on available adsorption site on GAC. EDCs/PhACs adsorption on GAC was determined as an endothermic reaction resulting in better adsorption at higher temperature ($40^{\circ}C$) than lower temperature ($10^{\circ}C$).

• Molecular & Cellular Toxicology
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• 제5권1호
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• pp.67-74
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• 2009

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

• 환경생물
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• 제18권3호
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• pp.291-298
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• 2000

난황형성(vitellogenesis)은 난생동물의 번식에서 매우 중요한 과정으로 간에서 난황전구물질(vitellogenin,Vg)의 생성과 단백질 수준에서 Vg의 변형과 난자내 축적 및 난황물질(vitellin)로의 전환을 포함한다. 난황은 경골어류의 배아의 영양물질 및 삼투압 조절을 통한 부유특성의 조절에 관여한다. 척추동물의 Vg유전자는 lipoprotein계열의 유전자로 복수의 Vg유전자가 존재하며 서로 다른 크기의 Vg단백질을 암호화한다. 에스트로젠에 의해 이들 단백질이 발현되는 정도에는 차이가 있다. 난생 척추 동물의 암컷에서 에스트로젠의 조절하에 생성되는 Vg은 천연 에스트로젠 및 합성에스트로젠에 의해 어류, 양서류, 파충류, 조류 등 다양한 척추동물의 수컷 체내에서도 형성되며 수온 및 생식주기에 의존적이다. 따라서 수컷에서 일어나는 난황전구물질의 생성은 환경오염물질 가운데 여성호르몬과 유사한 작용을 하는 물질의 규명과 위해성 여부를 판정할 수 있는 생물학적 지표로서 전세계적으로 이용되고 있다. 국내의 경우 Vg유도여부를 통한 야생생태계에서 환경호르몬 오염과 동물의 번식장애에 대한 연구에 있어서 번식주기, 동물의 지리적 분포와 생물다양성의 차이에 대한 고려가 중요하다.

• 미생물학회지
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• 제44권3호
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• pp.199-202
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• 2008

리그닌을 분해하는 백색부후균의 하나인 기계충버섯(Irpex lacteus)은 다양한 난분해성물질에 대한 분해능이 매우 높다. 그러나 이 균은 다양한 배양조건에서도 리그닌 분해효소의 하나인 laccase 활성이 매우 낮다. 난분해성 물질들에 대한 분해능을 향상시키기 위하여 laccase 활성을 증가시키고자 아교버섯의 laccase cDNA를 발현벡터로 구축하여 기계충버섯에 형질전환 방법으로 도입하였다. 항시 발현되는 glyceraldehyde-3-phosphate dehydrogenase 유전자의 프로모터와 재조합된 laccase 유전자는 생성된 형질전환체에서 배양초기인 생장기에서 강하게 발현되었으며, 생성된 형질전환체가 내분비장애물질의 하나인 비스페놀 A (BPA) 분해능은 물론 에스트로겐 활성 제거에 있어서도 더 우수하였다.

• Environmental Analysis Health and Toxicology
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• 제26권
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• pp.5.1-5.11
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• 2011

Objectives: In order to identify the possibility of slender bitterling (SB) (Acheilognathus yamatsutae) being used as a test species for estrogenic endocrine disrupting chemicals (EEDCs), we carried out the cloning and sequence characterization of the estrogen receptor (ER). Methods: The ER from a slender bitterling was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR), 5'- and 3'-rapid amplification of cDNA ends (5'-RACE and 3'-RACE) and T-vector cloning. The expression of ER mRNA was also analyzed in six tissues (brain, liver, kidney, gill, gonad, and intestines) by real-time PCR. Results: We obtained an ER from the slender bitterling. The SB ER cDNA was 2189 base pairs (bp) in length and contained a 1707 bp open reading frame that encoded 568 amino acid residues. The SB ER amino acid sequence clustered in a monophyletic group with the $ER{\alpha}$ of other fish, and was more closely related to zebrafish $ER{\alpha}$(88% identity) than to the $ER{\alpha}$ of other fish. The SB ER cDNA was divided into A/B, C, D, E and F domains. The SB ER has conserved important sequences for ER functions, such as the DNA binding domain (D domain), which are consistent with those of other teleosts. Conclusions: The ER of the slender bitterling could provide basic information in toxicological studies of EEDCs in the slender bitterling.

• 한국발생생물학회지:발생과생식
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• 제25권4호
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• pp.257-268
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• 2021

Phthalates and their metabolites are well-known endocrine disrupting chemicals. Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in industry and the exposing possibility to adult is high. In this study, DEHP was treated (133 ㎍/L and 1,330 ㎍/L in drinking water) according to the OECD test guideline 443 to mature female mice and their adrenal gland were examined for histological characteristics and steroidogenic gene expression. The wet weight of the adrenal gland was increased in all administrated groups compared to control. The diameter of zona fasciculata (ZF) was increased by DEHP in both outer ZF and inner ZF but there was no difference in morphology of the cells and arrangements into zona between groups. In addition, the arrangement of extracellular matrix was not different between control and DEHP groups. CYP11B1 was mainly localized at ZF and the intensity was not different between groups. DAX1 was localized in zona glomerulosa (ZG) and ZF, and its expression levels were decreased by DEHP administration. Its level was lower in DEHP133 group than DEHP1330 group. On the other hand, CYP17A1 was localized in ZG of DEHP1330 group. These results suggest that chronic low-dose DEHP exposing may modify the microstructure and function of the adrenal cortical cortex.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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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.