• The Korean Journal of Physiology and Pharmacology
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• 제19권1호
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• pp.73-79
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• 2015

Connexins (Cx) are membrane proteins and monomers for forming gap junction (GJ) channels. Cx46 and Cx50 are also known to function as conductive hemichannels. As part of an ongoing effort to find GJ-specific blocker(s), endocrine disruptors were used to examine their effect on Cx46 hemichannels expressed in Xenopus oocytes. Voltage-dependent gating of Cx46 hemichannels was characterized by slowly activating outward currents and relatively fast inward tail currents. Bisphenol A (BPA, 10 nM) reduced outward currents of Cx46 hemichannels up to ~18% of control, and its effect was reversible (n=5). 4-tert-Octylphenol (OP, $1{\mu}M$) reversibly reduced outward hemichannel currents up to ~28% (n=4). However, overall shapes of Cx46 hemichannel current traces (outward and inward currents) were not changed by these drugs. These results suggest that BPA and OP are likely to occupy the pore of Cx46 hemichannels and thus obstruct the ionic fluxes. This finding provides that BPA and OP are potential candidates for GJ channel blockers.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.135-135
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• 2003

Bisphenol A (BPA) mimics estrogen and its activity is one third to one quarter that of estradiol. BPA, an ubiquitous environmental contaminent has been shown to cause development reproductive toxicity and carcinogenic effect. BPA may do physiological action through ER${\alpha}$ and ER${\beta}$ which are expressed in central nerve system.(omitted)

• Environmental Analysis Health and Toxicology
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• 제24권4호
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• pp.287-292
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• 2009

Over the a few decades, the incidences of obesity and associated metabolic syndrome diseases have been increased dramatically and resulted in a global health crisis. Recent findings suggest endocrine disrupting chemicals (EDCs) as an obesogen, because they disrupt normal development and homeostatic controls over adipogenesis and energy balance in obesity. Furthermore, risk of cardiovascular disease and mortality is elevated among those who were obese during childhood. Thus, we focused on etiology of obesity in children and performed biological monitoring of bisphenol A (BPA), which is a broadly exposed EDC in environment. Study subjects were age and sex-matched obese and normal children in Seoul (N=52; age, $8.67{\pm}1.46$ years). Exposure levels of BPA were analyzed with HPLC/FLD as a conjugated form in urine. As results, ranges of urinary BPA were 0~54.38 ${\mu}g/g$ creatinine (median, 4.57 ${\mu}g/g$ creatinine). Levels of urinary BPA were 1.7 fold higher in the obese children than those in the controls (medians of obese and control children, 7.31 and 4.25 ${\mu}g/g$ creatinine, respectively, p=0.22). In the near future, enlarge scaled studies should be performed to confirm the risk of BPA for obesity.

• Toxicological Research
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• 제17권3호
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• pp.225-234
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• 2001

The present study was conducted to investigate the effects of Korean red ginseng water extract (KRGWE) on developmental toxicity caused by the environmental estrogen bisphenol A (BPA) in Sprague-Dawley rats. fifty males successfully mated were randomly assigned to five experimental groups, 1.e., group I (vehicle control), group II (BPA 1000mg/kg), group III (KRGWE 400mg/kg), group IV (BPA 1000mg/kg & KRGWE 200mg/kg), and group V (BPA 1000mg/kg & KRGWE 400mg/kg). The test articles were administered by gavage to mated females from gestational days (GD) 1 through 20 (sperm vaginal lavage=day O). All females were subjected to caesarean section on GD 21 and their fetuses were examined for external, visceral, and skeletal abnormalities. In the group II, significant maternal toxic effects including suppressed body weight, decreased body weight gain during pregnancy, and reduced food consumption were observed in pregnant rats. The minimal developmental toxicity including fetal ossification delay was also found in fetuses. In addition, a tendency for increased pregnancy failure, increased pre-and postimplantation loss, and decreased fetal body weight was observed. However, no fetal morpho-logical abnormalities were seen in surviving fetuses at a dose level of 1000mg BPA/kg. On the other hand, the maternal toxicity and developmental toxicity found in the groups IV and V were comparable to those of the group II. There were no adverse signs of either maternal toxicity or developmental toxicity in the group III. These results showed that administration of BPA at a dose level of 1000mg/kg to pregnant rats resulted in significant maternal toxicity and minimal developmental toxicity, and that no protective effects on BPA-induced maternal toxicity and developmental toxicity were found by concomitant gavage dosing of KRGWE.

• 한국환경보건학회지
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• 제47권1호
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• pp.87-100
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• 2021

Objectives: The purpose of this study was to analyze the factors affecting Bisphenol A (BPA) exposure in children and adolescents using the results of the Korean National Environmental Health Survey (KoNEHS) cycle 3. Methods: A total of 2,380 subjects (n=571, 887, and 922 for 3-5, 6-11, and 12-17 years of age, respectively) were analyzed using an environmental exposure survey and environmental chemical substances concentration levels. Univariable linear regression analysis was performed to determine associated variables such as sex, age, income level, housing type, secondhand smoke time, cup noodles and canned food consumption, seafood consumption, new furniture (within the previous six months), drinking water type, and consumption of herbal medicines. Variables with p-values of less than 0.2 were extracted from the results and a multivariable linear regression analysis was performed using stepwise selection. Results: Univariable linear regression analysis showed positive associations between BPA concentration levels and variables including sex, age, secondhand smoke time, new furniture (within the previous six months), renovated living space (within the previous six months), fish and shellfish consumption, plastic-bottled drink consumption, and herbal medicine. As a result of performing multivariable linear regression analysis, the lower was the age the higher was the concentration of BPA levels. Additionally, women showed higher BPA levels than those of men. The more frequently fish was consumed, the higher was the BPA concentration. Moreover, higher BPA concentrations were observed when taking herbal medicine. Conclusions: The main factors affecting BPA concentration levels were age, gender, and consumption of fish and herbal medicine.

• 한국발생생물학회지:발생과생식
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• 제27권4호
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• pp.195-203
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• 2023

Exposure to environmental chemicals, including endocrine-disrupting chemicals, during the gestational period can have profound adverse effects on several organs in offspring. Bisphenol A (BPA) can infiltrate the human body through food and drinks, and its metabolites can cross both the placental and the blood-brain barriers. In this study, we investigate the effect of gestational exposure to BPA on epigenetic, biochemical, and histological modifications in the uterine tissues of F1 adult offspring rats. Pregnant rats were exposed to BPA from gestational day 8-15, and changes in global DNA methylation in uterine tissues obtained from adult offspring born to the exposed mothers were analyzed. Global DNA methylation analysis revealed that gestational exposure to BPA resulted in DNA hypomethylation in the uterus. Progesterone receptor (PR) protein expression in uterine tissues was monitored using western blot analysis, which revealed that the PR protein content was considerably higher in all BPA-exposed groups than in the control. Immunohistochemical examination for the PR revealed that intense PR-positive cells were more frequently observed in the BPA-exposed group than in the control group. To date, the evidence that the upregulation of PRs observed in the present study was caused by the non-methylation of specific PR promoter regions is lacking. Conclusively, these results indicate that exposure to BPA during gestation induces epigenetic alterations in the uteri of adult female offspring. We speculate that the global DNA hypomethylation and upregulation of the PR observed simultaneously in this study might be associated with the uterus.

• Animal cells and systems
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• 제6권1호
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• pp.75-80
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• 2002

A study on the effects of bisphenol A (BPA) on sex differentiation and gonadal development in medaka, Oryzias latipes, was investigated by histological examination. The fish were exposed to aqueous solutions of BPA at nominal concentrations of 50, 100, and 200 $\mu\textrm{g}$/L from newly-hatched larvae stage to 70 d. The ovaries of female fish were composed of oocytes at the chromatin nucleolus and peri-nucleolus stages at 20 d after the exposure. The testes contained a number of spermatogonia and spermatocytes at 30 d. In the process of sex differentiation. gonadal development was not different in all experimental groups until 30 d after the exposure. At 70 d after the exposure, however, advanced development of oocytes in the ovary and inhibition of spermatogenesis in the testis were observed in the BPA-treated groups compared to the non-treated controls. More females than males were identified in the 50 and 100 $\mu\textrm{g}$/L BPA-treated groups, in comparison to the 200 $\mu\textrm{g}$/L BPA-treated group and non-treated controls. Medaka exposed to 200 $\mu\textrm{g}$/L BPA were bigger compared to other experimental groups. The present study suggests that BPA may lead to problems in either mating or sexual behavior due to the difference in growth and disparity of sexual maturation between male and female fish.

• 한국수산과학회지
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• 제37권3호
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• pp.192-196
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• 2004

The in vitro effect of bisphenol A (BPA) on ovarian steroidogenesis of the longchin goby (Chasmichthys dolichognathus) was investigated. Oocytes taken during the maturing phase (vitellogenic, fully vitellogenic or germinal vesicle breakdown stage) were incubated with BPA (100 ng/mL) in the presence of exogenous precursor $^{3}H-17\alpha\;hydroxyprogesterone\;(^{3}H-17\alphaOHP).$ Steroids were extracted from the media and the isolated oocytes, and the extracts were separated and identified by thin layer chromatography and gas chromatography-mass spectrometry. The identities of the major metabolites were progestogens $[17{\alpha}-hydroxy,20{\alpha}-dihydroprogesterone\;(17{\alpha}20{\alpha}OHP)\;and\;17{\alpha}-hydrxy,20{\beta}-dihydroprogesterone\;(17{\alpha}20{\beta}OHP),$ androgens [androstenedione (A4) and testosterone (T)] and estrogens [estrone $(E_1)\;and\;estradiol-17{\beta}(E_2)].$ BPA treatment inhibited production of estrogens in all the maturing phases and progestogens in the germinal vesicle migrating stage. Percentage yield of estrogens was decreased with increased yield of androgens. In conclusion, BPA had an inhibitory effect on the conversion of $^3H-17\alphaOHP$ to estrogens and progestogens. These results demonstrate that BPA can act either estrogenic or anti-estrogenic effects.

• 한국환경농학회지
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• 제39권4호
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• pp.375-383
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• 2020

BACKGROUND: Bisphenol A (BPA) is a chemical widely used in polycarbonate plastics, epoxy resins. BPA is an endocrine disruptor. Residue of BPA in agricultural environments is a major concern. The objective of this study was to understand the characteristics of the uptake and distribution of BPA and its metabolites introduced into the agricultural environment to crops, and to use it as basic data for further research on reduction of BPA in agricultural products. METHODS AND RESULTS: This study established the analysis method of BPA and its metabolites in soil and crops, and estimated the intake of BPA and its metabolites from lettuce (Lactuca sativa) grown in sandy loam and loam soil, which are representative soils in Korea. The two major metabolites of BPA were 4-hydroxyacetophenone (4-HAP) and 4-hydroxybenzoic acid (4-HBA). BPA, 4-HAP and 4-HBA have been analyzed by using liquid chromatography tandem mass spectrometry (LC-MS/MS). These substances were detected in sandy loam and loam soil, indicating that certain portions of BPA were converted to 4-HAP and 4-HBA in the soil; however, it was observed that only 4-HBA migrated to lettuce through the roots into crops. CONCLUSION: The uptake residues showed the BPA and 4-HAP were not detected in lettuces grown on sandy loam (SL) and loam (L) soil treatments that were applied with of 10 ng/g, 50 ng/kg and 500 ng/g of BPA. However, the 4-HBA was detected at the level of 7 ng/g and 11 ng/g in the lettuce grown in sandy loam and loam soil that were treated with the 500 ng/g of BPA, respectively, while the 8 ng/g of 4-HBA was measured in the lettuce cultivated in the loam that was treated with 100 ng/g of BPA. This result presents that the BPA persisting in the soil of the pot was absorbed through the lettuce roots and then distributed in the lettuce leaves at the converted form of 4-HBA, what is the oxidative metabolite of BPA.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.107.2-107.2
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• 2003

Bisphenol A(BPA) is a monomer widely used in the manufacturing polycarbonate plastic or epoxy resin and Mancozeb (MCZ), a polymeric complex of zinc and manganese salts of ethylene bisthiocarbamate, is widely used in agriculture as fungicide, insecticide and herbcide. These chemicals have been recently known as endocrine disruptors. To investigate the effects of BPA and MCZ on LPS-induced cytokine production (TNF-${\alpha}$) in vivo, female ICR mice were administered to various concentration of these materials (BPA; 100, 500, 1000 mg/kg/day, and MCZ; 250, 500, 1000, 1500 mg/kg/day) for 30 days and serum cytokine levels were measured at 1h post LPS injection (day 32) in BPA- or MCZ-administered mice. (omitted)