• Journal of Ginseng Research
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• v.44 no.3
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• pp.519-526
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• 2020

Background: Bisphenol A (BPA), known as an endocrine disruptor, is widely used in the world. BPA is reported to cause inflammation-related diseases. Korean Red Ginseng (KRG) has been used safely in human for a long time for the treatment of diverse diseases. KRG has been reported of its mitigating effect on menopausal symptoms and suppress adipose inflammation. Here, we investigate the protective effect of orally administered KRG on the impacts of BPA in the liver and uterus of menopausal mice model. Methods: The transcriptome analysis for the effects of BPA on mice liver was evaluated by Gene Expression Omnibus (GEO) database-based data (GSE26728). In vivo assay to evaluate the protective effect of KRG on BPA impact in ovariectomized (OVX) mice were designed and analyzed by RNA sequencing. Results: We first demonstrated that BPA induced 12 kinds of gene set in the liver of normal mice. The administration of BPA and KRG did not change body, liver, and uterine weight in OVX mice. KRG downregulated BPA-induced inflammatory response and chemotaxis-related gene expression. Several gene set enrichment analysis (GSEA)-derived inflammatory response genes increased by BPA were inhibited by KRG in OVX mice. Conclusion: Our data suggest that BPA has commonly influenced inflammatory response effects on both normal and OVX mice. KRG protects against BPA impact of inflammatory response and chemotaxis in OVX mouse models. Our comparative analysis will provide new insight into the efficacy of KRG on endocrine disrupting chemicals and OVX mouse.

• Journal of Microbiology and Biotechnology
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• v.17 no.3
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• pp.398-402
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• 2007

Abstract Female mice post weaning were exposed to 20 kHz sawtooth electric and magnetic fields (EMF) with $6.25{\mu}T$ peak intensity for 6 weeks. Estrous cycles were checked using vaginal smears over the last 10 days of the experimental period. The vaginal smears from EMF-exposed mice revealed an increase in the frequency of one or two phases persisting. The number of estrous cycles less than 1 was more in the EMF-exposed group than in the sham control group. Furthermore, in the EMF-exposed group, the duration of proestrous and metestrous stages of the estrous cycle was significantly increased compared with the control group. In conclusion, our results suggest that exposure to 20 kHz sawtooth EMF may affect normal cycling of the estrous cycle by disrupting the female reproductive endocrine physiology. We should not disregard the possible adverse reproductive effect of the 20 kHz sawtooth EMF generated under the occupational exposure situation in females.

• Toxicological Research
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• v.31 no.4
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• pp.331-337
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• 2015

Synthetic pyrethroids (SPs) are the most common pesticides which are recently used for indoor pest control. The widespread use of SPs has resulted in the increased exposure to wild animals and humans. Recently, some SPs are suspected as endocrine disrupting chemicals (EDCs) and have been assessed for their potential estrogenicity by adopting various analyzing assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LC) and cypermethrin (CP), the most commonly used pesticides in Korea, using BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To evaluate the estrogenic activities of two SPs, LC and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT-PCR) in LC or CP treated BG-1 ovarian cancer cells. In MTT assay, LC ($10^{-6}M$) and CP ($10^{-5}M$) significantly induced the growth of BG-1 cancer cells. LC or CP-induced cell growth was antagonized by addition of ICI 182,720 ($10^{-8}M$), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT-PCR results showed that transcriptional level of cyclin D1, a cell cycle-regulating gene, was significantly up-regulated by LC and CP, while these effects were reversed by co-treatment of ICI 182,780. However, p21, a cyclin D-ckd-4 inhibitor gene, was not altered by LC or CP. Moreover, $ER{\alpha}$ expression was not significantly changed by LC and CP, while down-regulated by E2. Finally, in xenografted mouse model transplanted with human BG-1 ovarian cancer cells, E2 significantly increased the tumor volume compare to a negative control, but LC did not. Taken together, these results suggest that LC and CP may possess estrogenic potentials by stimulating the growth of BG-1 ovarian cancer cells via partially ER signaling pathway associated with cell cycle as did E2, but this estrogenic effect was not found in in vivo mouse model.

• The Korean Journal of Pesticide Science
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• v.16 no.2
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• pp.187-193
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• 2012

Acute toxicity, water resolvability and short term reproduction test on Japanese medaka (Oriyzias latipes) for evaluating alachlor susceptibility to endocrine system were studied. Alachlor is known for suspected endocrine distruptors. As the results of tests, $LC_{50}$ (Median lethal concentration) was determined as 2.36 (1.994~2.805) mg/L, and test water replaced at 7 day intervals as its water resolvability was less than 20% in 7 days. The short term reproduction tests on Japanese medaka (Oriyzias latipes) were performed with a solvent control group, a treated group (alachlor concentrations of 0.02, 0.04, 0.11, 0.27, 0.68 ppm) and a positive control group (17 ${\beta}$ estradiol, 0.01, 0.1, 0.5 ppb). The number of spawning and embryo rates were declined in a alachlor-dose dependent manner, and the number of unfertilized eggs rates were in contrast increased depending on the concentrations. Further study should be needed to confirm whether the adverse effects may be effected by the concentrations. Additionally, alachlor was evaluated as a non-vitellogenin by the result of a test of significance of the vitellogenin content test for determination of the effect of estrogen among the endocrine disruptors.

• Journal of Environmental Health Sciences
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• v.32 no.1 s.88
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• pp.60-66
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• 2006

Bisphenol A(BPA) was known as an endocrine disrupting chemical. This study was conducted to assess the effect of BPA, weaker estrogen, on the preneoplastic and neoplastic lesions induced by diethylnitrosamine (DEN). One hundred male F344 rats were divided into four groups which were treated with DEN followed by BPA. To make liver tumor early, we conducted that DEN containing osmotic pump implanted into rat abdominal cavity. Then diet containing BPA were fed to the rats. All animals were sacrificed at 10 and 18 weeks. Body weights were significantly decreased in 4000ppm at 18 weeks. Relative Liver weights of 4000 ppm BPA treated group were significantly increased compared to that of DEN alone group at 18 weeks. There were no significant differences of liver tumor incidences. Sum area of GST-P positive foci and BrdU labeling indices of BPA treated group were not significantly different compared to those of control group. These results suggest that BPA have no effects in preneoplastic and neoplastic lesions on DEN-induced hepatocarcinogenesis.

• Development and Reproduction
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• v.26 no.4
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• pp.175-182
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• 2022

Previous studies, including our own, indicate that distinct morphological changes in rodent adrenal cortex could be induced by exposure of endocrine disrupting chemicals (EDC). In the present study, we conducted histological analyses of adrenocortical substructure using a nonylphenol-treated F1 rat model. The adrenal weight of NP-5000 group was significantly declined in female rats (p<0.001), while the adrenal weights of NP-treated groups were not significantly changed in male rats. The thickness of zona glomerulosa layers of female rats in NP-5000 group was significantly declined (p<0.001) but zona fasciculata layers were not changed. The zona reticularis layers of NP-treated group were significantly thinner than those of control group (NP-50, p<0.05; NP-5000, p<0.01). In male adrenal glands, there was no significant change of zona glomerulosa layers in NP-treated groups while the thickness of zona fasciculata in NP-5000 group was significantly decreased (p<0.01). Like female rats, the thickness of zona reticularis in NP-treated groups was significantly decreased (NP-50, p<0.001; NP-5000, p<0.05). Present study demonstrated that the adrenal histology could be altered by low-dose NP exposure in F1 rats, and the effect might be sexually dimorphic. Further study will be helpful for understanding possible adrenal pathophysiology induced by EDC exposure, and EDC-related sexually dimorphic phenomena in rodent adrenals.

• The Korean Journal of Pesticide Science
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• v.7 no.3
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• pp.188-197
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• 2003

Endocrine disrupting chemicals (EDCs) can alter hormone regulation that control reproductive system in animals. The effects of endosulfan, molinate, and alachlor that suspected to have examined disruption EDCs effect on a fish species of interest, Xiphophorus helleri (swordtail fish), were studied using vitellogenin (Vtg) and aromatase as diagnostic biomarkers. Induction of Vtg proteins was detected by RT-PCR in male fish treated with alachlor, and mixture of endosulfan and molinate in dose response manner. Also, induction of aromatase was detected by RT-PCR in male fish treated with alachlor, endosulfan, and mixture of endosulfan and molinate in sinlilar manner. In this study, swordtail fish exposed to endosulfan or molinate individually did not show any adverse effects. However, Vtg and aromatase expressions and apoptosis were detected in swordtail. fish exposed to the mixture of endosulfan and molinate. These results suggested that low concentrations of mixture of molinate and endosulfan individually do not affect swordtail fish, but may influence genital system, and induce apoptosis.

• Journal of Marine Life Science
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• v.5 no.2
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• pp.35-42
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• 2020

17β-estradiol (E₂) is a natural hormone secreted by ovary, and continuously discharged from household and livestock wastewater into aquatic environment. Due to its strong estrogenic activity, it has adverse effects on development and reproduction in crustacean as an endocrine disrupting chemical. Although ecdysteroid signaling pathway play a key role in development in crustacean, little information on transcriptional modulation of ecdysteroid-related genes in response to E₂ is available in small crustacean. Here, we investigated the acute toxicity of E₂ to obtain 24-h LC_x values in the brackish water flea Diaphanosoma celebensis. Time-dependent expression patterns of seven ecdysteroid pathway - related genes (CYP314a1, EcRA, EcRB, USP, ERR, Vtg, VtgR) were further examined using quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR). As results, 24-h LC₅₀ and LC₁₀ values were 9.581 mg/l and 4.842 mg/l, respectively. The mRNA expression of CYP314a1, EcRA, USP, VtgR was significantly up-regulated at 12 or 24 h after exposure to E₂. These findings indicate that E₂ can affect their molting and reproduction by modulating the expression of ecdysteroid pathway - related in D. celebensis. This study will be useful for better understanding of molecular mode of action of endocrine disrupting chemicals on molting process in small crustacean.

• Environmental Mutagens and Carcinogens
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• v.21 no.1
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• pp.34-43
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• 2001

Di-2-ethylhexyl phthalate (DEHP) is the most commonly used phthalate ester in polyvinyl chloride formulations including food packing and storage of human blood. DEHP is a well known as non-genotoxic carcinogen and endocrine disrupting chemical (EDC). DEHP have shown all negative results in ICH-guildeline recommended standard genotoxicity test battery. In this study, to assess the clastogenic and DNA damaging effect in human-derived tissue specific cells, DEHP was treated in human derived MCE-7 cells, HepG2 cells, LNCap cells, BeWo cells, MCE-10A cells, and female peripheral blood cells using micronucleus assay and in human breast carcinoma MCF-7 cells up to $1.28$\times$10^{-2}$ M using Comet assay. The in vitro micronucleus assay is a mutagenicity test system for the detection of chemicals which induce the formation of small membrane bound DNA fragment i.e. micronuclei in the cytoplasm of interphase cells, originated from clastogenic and/or aneugenic mechanism. The single cell gel electrophoresis assay (Comet assay) is used to detect DNA strand-breaks and alkaline labile site. In our results, DEHP increased significantly and/or dose-depentently and time-dependently micronucleus frequency at the 6 and 24 hr without metabolic activation system only in MCE-7 cells. DEHP treated with 2 hrs in MCF-7 cells using Comet assay induced DNA damage dose-depentantly.

• Journal of Korean Society on Water Environment
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• v.26 no.6
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• pp.948-953
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• 2010

In this study, degradation of estrone (E1) and $17{\alpha}$-ethynylestradiol (EE2) by gamma-irradiation and subsequent reduction of estrogenic activity as a function of absorbed dose were conducted using the yeast two-hybrid assay. Relative potency of E1 and EE2 compared to estrogenic activity of $17{\beta}$-estradiol (E2) was found to be 0.0144 and 0.1605, respectively. More than 90% of E1 and EE2 (both $5.0{\times}10^{-6}M$) was removed at an absorbed dose of 5 kGy, but more than 40% of estrogenic activity still remained. The addition of $TiO_2$ catalyst appeared to improve the removal efficiency of E1 and decrease estrogenic activity while there was no significant effect for EE2. Additionally, the calculated estrogenic activity of E1 and EE2 based on a regression model was well correlated with the observed activity.