• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.119-121
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• 2002

인류는 1,500 만 종류에 달하는 화학물질을 합성 혹은 분리ㆍ동정 해왔다. 그리고 현재 약 10 만 종류 정도의 화학물질이 상업적으로 이용되고 있다. 이들 화학물질 중에 유기염소화합물, 공업용화합물, 농약류, 유기취소(bromine)화합물, 중금속 및 유기금속, 식물 및 합성에스트로겐 등을 포함한 수십 종의 화합물이 내분비계장애물질 (Endocrine Disruptors, EDs)로서 생각, 혹은 의심되고 있다. 그러나, 대부분의 다른 화합물에 대해서는 그것들이 내분비계장애 작용을 가지고 있는지에 대한 충분한 지견이 얻어지지 않고 있어 이들 화학물질의 내분비계장애 작용을 평가하기 위해서는 신속 또는 간편한 검출계의 확립은 매우 중요하다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.184-184
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• 2003

Endosulfan is one of the organochlorine pesticides, well-known endocrine disruptors (EDs). Many EDs show the estrogenic effect. Estrogen is a group of hormones that play an important role in mammary gland function and implicated in mammary carcinogenesis. In the present study. using mouse mammary gland organ culture (MMOC) system. we studied the the effects of endosulfan on nodule like alveolar lesion (NLAL) formation in the mouse mammary gland development. (omitted)

• Journal of Microbiology and Biotechnology
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• 제20권11호
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• pp.1563-1570
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• 2010

To construct a highly sensitive detection system for endocrine disruptors (EDs), we have compared the activity of promoters with the n-alkane-inducible cytochrome P450 gene (ALK1), isocitrate lyase gene (ICL1), ribosomal protein S7 gene (RPS7), and the translation elongation factor-1${\alpha}$ gene (TEF1) for the heterologous gene in Yarrowia lipolytica. The promoters were introduced into the upstream of the lacZ or hERa reporter genes, respectively, and the activity was evaluated by ${\beta}$-galactosidase assay for lacZ and Western blot analysis for hER${\alpha}$. The expression analysis revealed that the ALK1 and ICL1 promoters were induced by n-decane and by EtOH, respectively. The constitutive promoter of RPS7 and TEF1 showed mostly a high level of expression in the presence of glucose and glycerol, respectively. In particular, the TEF1 promoter showed the highest ${\beta}$-galactosidase activity and a significant signal by Western blotting with the anti-estrogen receptor, compared with the other promoters. Moreover, the detection system was constructed with promoters linked to the upstream of the expression vector for the hER${\alpha}$ gene transformed into the Y. lipolytica with a chromosome-integrated lacZ reporter gene under the control of estrogen response elements (EREs). It was indicated that a combination of pTEF1p-hER${\alpha}$ and CXAU1-2XERE was the most effective system for the $E_2$-dependent induction of the ${\beta}$-galactosidase activity. This system showed the highest ${\beta}$-galactosidase activity at $10^{-6}\;M\;E_2$, and the activity could be detected at even the concentration of $10^{-10}\;M\;E_2$. As a result, we have constructed a strongly sensitive detection system with Y. lipolitica to evaluate recognized/suspected ED chemicals, such as natural/synthetic hormones, pesticides, and commercial chemicals. The results demonstrate the utility, sensitivity, and reproducibility of the system for identifying and characterizing environmental estrogens.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.169-169
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• 2002

The present was performed to identify the effects of tributyltin oxide (TBTO) in the immature mice testes. 3-week-old male ICR mice were orally administrated on one time basis of TBTO dose of 0 (Vehicle control, VC), 30 (TBTO 30 mg/kg, T30), 60 (TBTO 60 mg/kg, T60) per each one.(omitted)

• 한국환경과학회지
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• 제20권2호
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• pp.231-239
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• 2011

Diethyl phthalate (DEP) and nonylphenol (NP) are widely spread in the natural environment as an endocrine disruption chemicals (EDs). Therefore, in this study, ultrasound (US) and ultraviolet (UVC), including $TiO_2$, as advanced oxidation processes (AOPs) were applied to a DEP and NP contaminated solution. When only the application of US, the optimum frequency for significant DEP degradation and a high rate of hydrogen peroxide ($H_2O_2$) formation was 283 kHz. We know that the main mechanism of DEP degradation is radical reaction and, NP can be affected by both of radical reaction and pyrolysis through only US (sonolysis) process and combined US+UVC (sonophotolysis) process. At combined AOPs (sonophotolysis/sonophotocatalysis) such as US+UVC and US+UVC+$TiO_2$, significant degradation of DEP and NP were observed. Enhancement effect of sonophotolysis and sonophotocatalysis system of DEP and NP were 1.68/1.38 and 0.99/1.17, respectively. From these results, combined sonophotocatalytic process could be more efficient system to obtain a significant DEP and NP degradation.

• 한국발생생물학회지:발생과생식
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• 제4권1호
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• pp.53-59
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• 2000

내분비계 장애물질은 생체내에서 호르몬 등의 내분비계에 영향을 주기 때문에 미량으로도 생식기능에 이상을 가져 올 수 있고, 급ㆍ만성 독성과는 달리 차세대에 그 영향이 발현될 수 있다. 대부분의 내분비계 장애물질은 에스트로겐 유사물질로 알려져 있으며, 내분비계 장애물질의 하나인 bisphenol A (BPA)도 이러한 성질을 가진 물질이다. 본 연구는 BPA가 생쥐의 정자형성과정에 어떤 영향을 미치는가를 분석하고자, 농도별 (저농도, 20 mg/kg, 고농도 200 mg/kg) 구강투여를 실시하였다. 정자수와 테스토스테론 농도 및 산자수가 대조군에 비해 처리군에서 점진적으로 감소하는 경향을 보였으며, 산자수에서 유의적인 차이(P<0.01)를 나타내었다. 특히 국부적이긴 하지만 세정관 내강에서의 정자세포 소실 양상은 정자수의 감소 원인으로 사료된다. 성성숙 이후 정소에서의 발현이 소실되는 것으로 알려진 TGF-$\beta$계에서는 TGF-$\beta$1이 고농도의 BPA투여시 발현되었지만, 그 외의 리간드와 수용체의 발현은 관찰되지 못했다. 결론적으로 고농도의 BPA노출은 웅성생식계에 영향을 미칠 수 있으며, 이는 정자형성에 장애를 일으켜 불임을 유발할 수도 있을 것으로 보여진다.

• Archives of Pharmacal Research
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• 제28권3호
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• pp.351-357
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• 2005

Endosulfan is one of the organochlorine pesticides, which are well-known endocrine disruptors (EDs), and it acts as an estrogen agonist. Estrogen is a group of hormones that play an important role in mammary gland function and are implicated in mammary carcinogenesis. In the present study, we studied the effects of endosulfan on nodule like alveolar lesion (NLAL) formation in mouse mammary gland development using a mouse mammary gland organ culture (MMOC) system. Although endosulfan-treated mammary glands did not form NLALs, more alveolar buds were formed in this group than in the negative control (vehicle-treated) group. In addition, telomerase reverse transcriptase (TERT) mRNA expression levels were increased in endosulfan-treated mammary glands in a dose-dependent manner. Telomerase can be activated by estrogen, therefore, we examined the effects of endosulfan on telomerase activity, and found that the telomerase activity in estrogen receptor-positive MCF-7 cells was up-regulated by endosulfan treatment. Moreover, this activation was accompanied by the up­regulation of the TERT mRNA expression. Also, transient expression assays using CAT reporter plasm ids containing various fragments of the TERT promoter showed that this imperfect palindromic estrogen-responsive element is almost certainly responsible for the transcriptional activation by endosulfan. These results may help elucidate the endocrine disrupting mechanism of endosulfan.

• Animal cells and systems
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• 제5권4호
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• pp.327-331
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• 2001

There is a critical developmental period during which brain sexual differentiation proceeds irreversibly under the influence of gonadal hormone. Recently, kinesin superfamily-associated protein 3 (KAP3) gene expressed during the 'critical period' of rat brain differentiation was identified by us (Choi and Lee, 1999). KAP3 functions as a microtubule-based motor that transports membranous organelles anterogradely in cells, including neurons (Yamazaki et al., 1996). mRNA level of KAP3 gene markedly increased before the initiation of puberty. Neonatal treatment of estrogen clearly inhibited the prepubertal increase in KAP3 mRNA level (Choi and Lee, 1999). In the present study, we aimed to investigate the effects of polychlorinated biphenyls (PCBs), as endocrine disruptors (EDs) on the expression of KAP3 gene during the 'critical period' of rat brain development. In our data, PCBs significantly decreased the expression of KAP3 gene in the fetal (day 17) and the neonatal (day 6 after birth in) male and female rat brains. The body weight and the breeding ability were significantly decreased in the PCBs-exposed rats compared with the control. These results showed that PCBs affect the transcriptional level of brain sexual differentiation related gene, KAP3, in the fetal and the neonatal rat brains. The maternal exposure to the PCBs may lead to toxic response in embryonic brain sexual differentiation and breeding ability after sexual maturation. This study indicates that KAP3 gene may be useful as a gene marker to analyze the molecular mechanism of toxic response in the animal brain development and sexual maturation exposed to PCBs.

• 한국환경생물학회:학술대회논문집
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• 한국환경생물학회 2002년도 학술대회
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• pp.33-37
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• 2002

The present was performed to identify the effects of tributyltin (TBT) in the immature mice testes. 3-week-old male ICR mice were orally administrated on one time basis of TBT dose of O (Vehicle control, VC), 25 (TBT 25 mg/kg, T$_{25}$ ), 50 (TBT 50 mg/kg, T$_{50}$ ), 100 (TBT 100 mg/kg, T$_{100}$ ) mg/kg per each one. After 3 days the time treated of TBT, mice were sacrified and wighted body, testis, epididymis, seminal vesicle, vas deferens, and prostate. As the result of weighing, wights of each oragan and gonad index were tendency decresed in comparing groups of TBT treated with that (C) of unteated (p <0.05). As the result of examination of steroid hormones in the immature male mice, The concentrations of serum and intratesticular testosterone were significatly increased rather than the control group. But concentrations of estradiol were decresed objectly. A group of the highest change of concentrations of steroid hormones is T$_{100}$ . The high dose group, T$_{100}$ , was decreased all of concentrations of steroid hormones rather than those of T$^{25}$ . The result of observation with histological changes in testis showed a tendency for innercellular wall to increase damage and extinction in seminiferous tubles. As the result of investigation apoptotic cell numbers in the testis using teminal deoxy-nucleotidyl transferase -mediated dUTP-digoxygenin nick end-labeling immunohistochemical straia, The ratio of Apoptic cells significantly was incensed in depending on treatment of TBT does. In conclusion, these results shows that TBT triggers apoptosis on reproductive cell in testis and changes level of concentrations of steroid hormones in the immature male mice , as endocrine disruptors (EDs).

• 한국환경생물학회:학술대회논문집
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• 한국환경생물학회 2005년도 추계학술대회 초록집
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• pp.22-35
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• 2005

내분비계 장애물질 (Endocrine Disruptors: EDs)이란 ‘내분비 기능에 변화를 일으켜, 생체 또는 그 자손의 건강에 위해한 영향을 미치는 외인성 물질’로서 세계야생생물보호기금 (World Wildife Fund: WWF)의 목록에는 67 여종, 일본 후생성에서는 142 여종의 물질을 내분비계 장애물질로 분류하고 있다. 이렇게 분류된 내분비계장애물질 가운데에는 많은 종류의 농약이 포함되어 있으며, 이들이 자연상태계에 미치는 영향에 대한 많은 보고가 있다. 양서류는 먹이연쇄의 중위포식자로 내분비계 장애물질의 순환 및 생채축적 회로에서 중요한 위치를 갖는다. 또한 농경지나 계류 등에 서식하며 산란하는 습성이 있다. 이러한 서식지는 농약 등에 노출받기 쉬우므로 환경오염평가 대상동물로 중요하다. 본 연구에서는 국내에서 사용되고 있는 제초제, 살충제 등이 양서류 발생에 미치는 영향을 평가하고, 이들 물질에 의한 노출을 평가할 수 있는 biomarker 유전자를 발굴하고자 하였다. 우리나라 전역에 많이 분포하는 무당개구리(Bombina orientalis)의 초기 배아발생 과정에서 이들 농약을 처리하였을 때, 물질의 종류에 따라 정도의 차이는 있으나 농도 의존적으로 배아 및 올챙이의 치사율이 높게 나타났다. 또한 농약은 배아 및 올챙이의 기형을 유발하였다. 기형의 종류는 농약에 따라 서로 상이한 형태로도 나타났으나, 특히 몸통휨 또는 꼬리휨등의 척추골 기형이 많이 나타났다. 환경 위해성 평가 biomarker 유전자로서 골격계 형성에 관여하는 Sox9 유전자를 선택하였다. 무당개구리에서 처음으로 Sox9 유전자를 동정하였으며, 농약을 처리한 실험군에서의 Sox9 유전자의 발현 양상은 대조군에 비하여 높게 나타났다. 본 연구결과 생태계에서 내분비계 장애물질의 위해성 평가를 위해 양서류 초기배아의 치사 및 기형의 정도를 관찰하는 방법이 유효할 것으로 사료된다. 또한 야생동물의 biomarker 유전자를 발굴과 이를 이용한 위해성 평가는 더욱 정밀한 평가법으로 유용할 것이다.