• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5445-5450
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• 2012

Although benign uterine leiomyomata (LMA) is the most common reproductive tumor in premenopausal women, its etiology is largely unknown. We aimed in the present study to demonstrate the potential role of environmental factors with estrogenic activity in tumor etiology by focusing on the role of aryl hydrocarbon receptor (AhR) which mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This case-control study aimed to compare the interactions between AhR and lifestyle factors in a clinical setting for the first time among 138 newly diagnosed LMA patients and 138 normal controls who lived in Tehran and Mashhad, respectively, during the last 10 years. To conduct immunohistochemical studies using appropriate monoclonal antibodies, 30 cases were selected retrospectively from 2009-2011 from the pathology departments of two university hospitals in Tehran. Although the levels of sex steroid receptors were similar in adjacent myometrium and uterine leiomyomas of all cases, AhR was significantly overexpressed (p=0.034, OR=1.667) in uterine LMA and this overexpression was correlated with living in Tehran [(p=0.04, OR=16 (1.216-210.58)], smoking[P=0.04, OR=2.085 (1.29-3.371)], living near polycyclic aromative hydrocarbon producing companies [p=0.007, OR=2.22 (1.256-3.926)] and eating grilled meat [p=0.042, OR=1.28 (1.92-3.842)]. Our study contributes to the understanding of the effects of EDCs on AhR levels as well as women's health and points out possible risk factors for the development and growth of uterine LMA. It seems that the development of LMA could be the result of interactions between hormonal and environmental factors.

• 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.

• 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.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.503-511
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• 2018

Triclosan (TCS) and bisphenol A (BPA) are endocrine-disrupting chemicals that interfere with the hormone or endocrine system and may cause cancer. Kaempferol (Kaem) and 3,3'-diindolylmethane (DIM) are phytoestrogens that play chemopreventive roles in the inhibition of carcinogenesis and cancer progression. In this study, the influence of TCS, BPA, Kaem, and DIM on proliferation and apoptotic abilities of VM7Luc4E2 breast cancer cells were examined. MTT assay revealed that TCS ($0.1-10{\mu}M$), BPA ($0.1-10{\mu}M$) and E2 ($0.01-0.0001{\mu}M$) induced significant cell proliferation of VM7Luc4E2 cells, which was restored to the control (0.1% DMSO) by co-treatment with Kaem ($30{\mu}M$) or DIM ($15{\mu}M$). Reactive oxygen species (ROS) production assays showed that TCS and BPA inhibited ROS production of VM7Luc4E2 cells similar to E2, but that co-treatment with Kaem or DIM on VM7Luc4E2 cells induced increased ROS production. Based on these results, the effects of TCS, BPA, Kaem, and DIM on protein expression of apoptosis and ROS production-related markers such as Bax and Bcl-xl, as well as endoplasmic reticulum (ER) stress-related markers such as $eIF2{\alpha}$ and CHOP were investigated by Western blot assay. The results revealed that TCS, and BPA induced anti-apoptosis by reducing ROS production and ER stress. However, Kaem and DIM effectively inhibited TCS and BPA-induced anti-apoptotic processes in VM7Luc4E2 cells. Overall, TCS and BPA were revealed to be distinct xenoestrogens that enhanced proliferation and anti-apoptosis, while Kaem and DIM were identified as natural chemopreventive compounds that effectively inhibited breast cancer cell proliferation and increased anti-apoptosis induced by TCS and BPA.

• Nutrition Research and Practice
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• v.18 no.5
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• pp.711-720
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• 2024

BACKGROUND/OBJECTIVES: The diet is an important route of exposure to endocrine-disrupting chemicals (EDCs). However, few studies have investigated the association between dietary intake and EDC exposure levels among Koreans. In an earlier study, we showed that the bioactivity of serum aryl hydrocarbon receptor ligands (AhRLs) could be a surrogate biomarker to indicate exposure to EDCs and that they inhibit mitochondrial function. We also found that the mitochondria-inhibiting substances (MIS) in serum ascertained by intracellular adenosine triphosphate (MIS-ATP) and reactive oxygen species (MIS-ROS) levels could be biomarkers of exposure to EDCs, as they showed a strong correlation with AhRL and the levels of EDCs in the blood. Here, we investigated the association between the consumption of specific foods and surrogate serum biomarkers for EDCs, namely AhRL, MIS-ATP, and MIS-ROS, among middle-aged Korean adults. SUBJECTS/METHODS: A total of 1,466 participants aged 45-76 yrs from the Ansung cohort of the Korean Genome and Epidemiology Study were included. Food consumption, including that of meat, fish, vegetables, and fruits, was measured using a semiquantitative food frequency questionnaire. RESULTS: Fish intake was positively associated with AhRL (β = 0.0035, P = 0.0166), whereas cruciferous vegetable intake was negatively associated with AhRL (β = -0.0007, P = 0.0488). Cruciferous vegetable intake was positively associated with the MIS-ATP levels (β = 0.0051, P = 0.0420). A higher intake of fish was significantly associated with an increased risk of high AhRL (tertile: odds ratio [OR], 1.49; 95% confidence intervals (CIs), 1.08-2.06; P for trend = 0.0305). In addition, the second-highest tertile of cruciferous vegetable intake had lower odds of high AhRL than the lowest tertile (OR, 0.73; 95% CIs, 0.54-0.97), although no significant linear trend was observed. CONCLUSION: Consumption of different types of foods may be differentially associated with EDC exposure in middle-aged Korean adults.

• Journal of Environmental Health Sciences
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• v.44 no.2
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• pp.115-123
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• 2018

Objectives: Preservatives, suspected to be endocrine disrupting chemicals, are widely used in feminine hygiene products for the prevention of deterioration. Information regarding the usage patterns of feminine hygiene products and the concentrations of preservatives in these products is limited. The present study was conducted to investigate the use of feminine cleansers among Korean women and quantify the concentration of preservatives in feminine cleansers. Methods: Approximately 500 women were recruited from the city of Busan in August 2017 and a questionnaire survey was conducted on the use of feminine cleansers. Several major feminine hygiene products (n=69) were identified and selected for analysis of 22 preservatives. Following appropriate preparation, the products were analyzed by HPLC/DAD. Results: Over 70% of the participating women used at least one feminine cleanser. Marital status and parity were associated with the frequency of use. Liquid was most frequently used form of feminine cleanser (66.6%). The greatest proportion of subjects answered that they use it 'one to two times per week' (36.5%). Among the 69 feminine cleansers, benzoic acid, sorbic acid, phenoxyethanol, and methyl paraben were detected at $144-4,428{\mu}g/g$, $195-1,470{\mu}g/g$, $269-4,237{\mu}g/g$, and $625-4,901{\mu}g/g$, respectively. BA was the most frequently detected (46.4%). Conclusions: In the present study, the characteristics of feminine cleanser use among Korean women were investigated. Based on an analysis of preservatives in the feminine hygiene products, one product was determined to exceed the maximum authorized concentration of MeP (0.4%). Our results will help refine exposure and risk assessment for toxic chemicals in feminine cleansers.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.10a
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• pp.173-173
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• 2003

With the introduction of DNA microarrays, a high throughput analysis of gene expression is now possible as a replacement to the traditional time-consuming Southern-blot analysis. This cDNA microarray should be ahighly favored technology in the area of molecular toxicology or analysis of environmental stresses.In this study, therefore, we developed a novel cDNA microarray for analyzing stress-specific responses in japanese Medaka fish. In the design and fabrication of this stress specific functional cDNA microarray, 123 different genes in Medaka fish were selected from eighteen different stress responsive groups and spotted on a 25${\times}$75 mm glass surface. After exposure of the fish to bisphenol A which is the one of the well-known endocrine disrupting chemicals (EDCs), over 1 or 10 days, the responses of the DNA chip were found to show distinct expression patterns according to the mode of toxic actions from environmental toxicants. As a results, they showed specific gene expression pattern to bisphenol A, additionally, the chemical spesific biomarkers could be suggested based on the chip analysis data. Therefore, this chip can be used to monitor stress responses of unknown and/or known toxic chemicals using Medaka fish and may be used for the further development of biomarkers by utilizing the gene expression patterns for known contaminants.

• Development and Reproduction
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• v.23 no.3
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• pp.263-275
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• 2019

Based on our preliminary results, we examined the possible role of low-dose and chronic-exposing of the chemicals those are known as endocrine disrupting chemical (EDC), on the proliferation of uterine endometrium and the localization of steroid receptors. Immunohistochemical or immunofluorochemical methodology were employed to evaluate the localization of antigen identified by monoclonal antibody Ki 67 protein (MKI67), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and progesterone receptor (PGR). In $133{\mu}g/L$ and $1,330{\mu}g/L$ di(2-ethylhexyl) phthalate (DEHP) and $50{\mu}g/L$ nonylphenol (NP) groups, the ratio of MKI67 positive stromal cells was significantly increased but not in $500{\mu}g/L$ NP group. The ratios of MKI67 positive glandular and luminal epithelial cells were also changed by the chronic administration of NP and DEHP in tissue with dose specific manner. ESR1 signals were localized in nucleus in glandular and luminal epithelia of control group but its localization was mainly in cytoplasm in DEHP and NP administered groups. On the other hand, it was decreased at nucleus of stromal cells in $1,330{\mu}g/L$ DEHP group. The colocalization patterns of these nuclear receptors were also modified by the administration of these chemicals. Such a tissue specific and dose specific localization of ESR2 and PGR were detected as ESR1 in all the uterine endometrial tissues. These results show that the chronic lows-dose exposing of NP or DEHP modify the localization and colocalization of ESRs and PGR, and of the proliferation patterns of the endometrial tissues.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.32 no.3
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• pp.253-267
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• 2022

Objectives: This study was performed to check whether the CRS (Chemical Ranking and Scoring) system is appropriate as a method to determine substances as candidates for substances subject to permission and to apply this system to the selection of candidates for substances subject to permission. Methods: A risk score was obtained by multiplying the hazard score and the exposure score and then ranking them. The hazard sub-indicators are carcinogenicity, germ cell mutagenicity, reproductive toxicity, specific target organ toxicity-repeated exposure, respiratory sensitization and endocrine disrupting chemicals. Exposure sub-indicators are persistence, bioaccumulation and emission volume. Sensitivity analysis was performed for missing values. Correlation analysis and multivariable linear regression analysis were performed among hazard, exposure and risk in order to confirm that CRS was an appropriate method. Results: As a result of the sensitivity analysis on missing values, it was confirmed that the effect on the risk ranking was not sensitive. Correlation and regression analysis confirmed that exposure had a greater effect on risk than hazard. Conclusions: The CRS system, which derives a risk score using a hazard and exposure score, is judged to be appropriate as a method for the selection of preliminary of candidates for substances subject to permission. Benzene, cadmium, nickel, and cobalt were selected as priority candidates for substances subject to permission.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.385-389
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• 2023

Background: Ginseng has been used as a traditional medicine for treatment of many diseases and for general health maintenance. Previously, we showed that ginseng did not demonstrate estrogenic property in ovariectomized mouse model. However, it is still possible that disruption of steroidogenesis leading to indirect hormonal activity. Methods: The hormonal activities were examined in compliance with OECD guidelines for detecting endocrine disrupting chemicals: test guideline (TG) No. 456 (an in vitro assay method for detecting steroidogenesis property) and TG No. 440 (an in vivo short-term screening method for chemicals with uterotrophic property). Results: Korean Red Ginseng (KRG) and ginsenosides Rb1, Rg1, and Rg3 did not interfere with estrogen and testosterone hormone synthesis as examined in H295 cells according to TG 456. KRG treatment to ovariectomized mice did not show a significant change in uterine weight. In addition, serum estrogen and testosterone levels were not change by KRG intake. Conclusion: These results clearly demonstrate that there is no steroidogenic activity associated with KRG and no disruption of the hypothalamic-pituitary-gonadal axis by KRG. Additional tests will be performed in pursuit of cellular molecular targets of ginseng to manifest mode of action.