• 한국발생생물학회지:발생과생식
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• 제21권2호
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• pp.121-130
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• 2017

4-Nonylphenol (NP) is a surfactant that is a well-known and widespread estrogenic endocrine disrupting chemical (EDC). Although it has been known that the affinity of NP to ERs is low, it has been suggested that low-dose NP has toxicity. In the present study, the endocrine disrupting effects on reproduction, and the weight of gonads, epididymis, and uterus were evaluated with the chronic lower-dose NP exposing. This study was designed by following the OECD test guideline 443 and subjected to a complete necropsy. In male, NP had an effect on the weight of the testis and epididymis in both $F_0$ and $F_1$. In females, NP decreased the weight of ovary and uterus in $F_0$ but not in pre-pubertal $F_1$ pubs. Fertility of male and female in $F_0$ or $F_1$ was no related with NP administration. The number of caudal-epididymal sperm by body weight (BW) was not different between groups in both $F_0$ and $F_1$. Besides, the difference of the sperm number between generations was not detected. The number of ovulated oocytes was similar between groups in $F_0$, but significantly decreased in NP 50 group of $F_1$. The litter size and sex ratios of offspring in $F_1$ and $F_2$ were not different. The accumulated mating rate and gestation period were not affected by the NP administration. Those results shows that chronic lower-dose NP administration has an effect of endocrine disruptor on the weight of gonads and epididymis of $F_0$ and $F_1$ but not in reproduction. Based on the results, it is suggested that chronic lower-dose NP exposing causes endocrine disruption in the weight of gonad and epididymis but not in the reproductive ability of next generations.

• 환경생물
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• 제22권4호
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• pp.532-536
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• 2004

Due to the fourth-instar larvae of C. riparius have a sensitive to ecdysteroidal molting hormones for the life cycle developments, accordingly the emerged adult affected corresponding to larval phase's environments. The emerged female from larval phase exposure to DEHP observed a fact body and clumsy fling behavior in females. The body volume of treated female groups was clearly larger than that of control fe- males. In the 2D/E gel 1108 protein spots were identified. The visualized protein spots allowed extraction of 27 protein spots differed more than 3 fold in DEHP treated animals, which was approximately 2.4％ of the total protein spots. In this view, the body volume (or morphological characters) was well observed and detected faster than physiological detection for various EDCs. In this study, the body volume as a detecting po-int for EDCs suggested a bio-marker in individual levels.

• Toxicological Research
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• 제21권4호
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• pp.333-338
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• 2005

Many of thyroid hormones disrupting chemicals induce effects via interaction with thyroid hormone and retinoic acid receptors and responsive elements intrinsic in target cells. We studied thyroid hormones disrupting effects of food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD, PCBs and TDBE in recombinant HeLa cells containing plasmid construct for thyroxin responsive elements. The limit of response of the recombinant cells to T3 and T4 was $1\times10^{-12}\;M$. BHA. genistein, cadmium and TBDE were interacted with thyroid receptors with dose-responsive pattern. In addition, BHA, BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, and TBDE showed synergism while cadmium chloride antagonism for T3-induced activity. This study elucidates that recombinant HeLa cell is sensitive and high-throughput system for the detection of chemicals that induce thyroid hormonal disruption via thyroid hormone receptors and responsive elements. Also this study raised suspect of BHA. BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, TBDE, genisteine and cadmium chloride as thyroid hormonal system disruptors.

• 환경생물
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• 제27권4호
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• pp.323-333
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• 2009

파라벤은 p-하이드록시 벤조산(p-hydroxybenzoic acid)의 알킬에스테르로, 비교적 빠르게 흡수, 대사 및 배설되는 살균성 보존제로 식품, 화장품, 약품 등에 널리 사용되고 있다. 실제 인체는 파라벤 복합물에 노출된다. 파라벤의 안전성에 관한 연구결과들에 대한 고찰 결과 파라벤 종류에 따라 다양한 독성종말점을 대상으로 파라벤의 급성, 아급성 및 만성독성 영향은 비교적 적은 것으로 나타났다. 파라벤은 에스트로젠 유사활성을 가지며 화장품을 통한 경피흡수를 통해 유방암과의 상관성이 보고되었으나, 이와 상반된 견해도 있다. 파라벤의 항안드로젠성은 남성생식기계의 장애를 유발할 수 있으나 이와 상반된 견해도 있다. 파라벤은 정자의 미토콘드리아 기능 및 남성호르몬 생성을 저해할 수 있으나 이와 상반된 견해도 있다. 배아발달에는 독성이 없는 것으로 나타났다. 세포독성으로는 세포용혈, 미토콘드리아 막투과성 변화, 세포사멸 등을 유발할 수 있다. 수환경에서 파라벤은 환경에스트로젠으로 작동하여 어류에서 내분비장애 효과를 발휘한다. 결론적으로 파라벤은 저독성물질로 분류할 수 있으나, 인체 및 수생동물들에서 파라벤의 노출경로 및 농도, 사용기간 등에 따른 독성과 내분비계장애 효과에 대하여는 다양한 종말점을 대상으로 좀 더 구체적인 독성자료들이 요구된다.

• 환경생물
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• 제32권4호
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• pp.271-285
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• 2014

알루미늄은 폐광산 침출수, 산업폐수, 생활하수 등을 통해 수계로 유입되어 수생생물에 농축되고 독성을 유발할 수 있다. 최근 다양한 수생생물에서 알루미늄의 독성에 관한 보고가 증가하고 있지만 오염현황 및 생태독성에 대한 연구가 많이 이뤄지지 않았다. 본 소고에서는 수서무척추동물, 어류, 양서류에서 알루미늄의 독성자료를 고찰함으로써 잔류량 가이드라인 설정의 필요성과 알루미늄의 수생태독성 분석전략을 제언하고자 하였다. 다양한 형태의 알루미늄화합물이 수생동물에서 1차적으로 아가미기능을 방해하여 생존을 위협하고 세포독성, 유전독성, 산화적스트레스, 내분비계교란, 생식교란, 대사교란, 항상성교란 등의 독성효과가 있는 것으로 확인되었다. 특히, 산성조건에서 환경잔류농도 수준의 알루미늄 화합물은 어류에서 호르몬농도 변화를 유발하였다. 알루미늄은 산성 및 염기성 조건에서 용해도가 증가하기 때문에 국내의 폐광산 인근의 산성 수계 뿐 아니라 조류 대발생에 의해 pH가 상승하는 호수나 강에서도 알루미늄의 독성효과가 나타날 것으로 사료된다.

• 생태와환경
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• 제38권1호통권110호
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• pp.11-17
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• 2005

야외에서 채집한 C. plumosus를 대상으로 잠재적 내 분비계 교란물질인 DEHP, BPA 및 Tebufenozide를 처리물질로 하여 형태적인 교란 효과를 살펴보았다. 약제에 노출된 개체의 하순기절은 부드러워지거나(smooth) 손실(loss)이 가장 많았으며 엷은 갈색을 보였다. 처리 물질에 따른 기형의 정도를 살펴보면, DEHP는 46.2 ${\sim}$ 85.7%, BPA는 73.7 ${\sim}$ 90.9% 그리고 tebufenozide는 57.6 ${\sim}$ 78.9%가 기형을 입어 BPA>tebufenozide>DEHP 순으로 기형이 크게 나타났다. 처리 물질별 기형 부위를 살펴보면, MIX (32 ${\sim}$ 46%)>MLT (25 ${\sim}$ 34%)>LT (3 ${\sim}$ 7%)로 두 부분이 함께 기형을 입는 형태가 가장 많았으며 LT 단독의 기형이 가장 적었다. MIX 형태로 기형이 가장 높은 물질은 BPA (46%)>DEHP (33%)>tebufenozide (32%)이고, MLT에 가장 높은 기형을 보인 것은 DEHP (34%)>tebufenozide (31%)>BPA (25%)로 나타났다. Tebufenozide 처리에 따른 하순기절의 색은 처리 농도가 높아지면 엷은 갈색 하순기절의 발생 빈도가 증가되었다 (27.8 ${\sim}$ 84.2%). 반면, BPA (8.7%)와 DEHP (18.2%)는 $1\;{\mu}g\;L^{-1}$에서 가장 낮은 엷은 갈색의 하순기절의 발생 빈도를 보였으나 $0.3\;{\mu}g\;L^{-1}$처리에서는 매우 높은 엷은 갈색의 하순기절이 다수 발생하였다 (BPA 52.6%; DEHP 30.8%).

• Journal of Ginseng Research
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• 제47권3호
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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.

• Toxicological Research
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• 제31권4호
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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.

• 한국환경보건학회지
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• 제29권2호
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• pp.7-15
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• 2003

DEHP는 대표적인 플라스틱 가소제 가운데 하나로서, 광범위하게 사용되고 있으며, 내분비계 장애물질로 분류퇴고 있다. 실제로 하천, 해양, 토양 등 광범위한 환경에서 검출되고 있지만, 이 물질이 수서 생물에 미치는 내분비교란 영향과 기작에 대해서는 거의 알려진 바가 없다. 본 연구에서는 송사리로 불리우는 Oryzias latipes(Japanese medaka)와, 유생 시기에 저니성 무척추 동물로 존재하다가 성충이 되는 Chironomus riparius를 대상으로 DEHP가 내분비 장애물질로서 생식작용에 미치는 영향에 대하여 연구하였다. 먼저, Japanese medaka를 부화 직후부터 3개월간 DEHP 1, 10, 50 $\mu\textrm{g}$/l의 농도로 노출시킨 결과 암놈의 혈중 비텔로제닌의 감소 ,생식소 지수인 GSI(Gonado Somatic Index) 감소. 난자 발달 저해 등이 관찰되었다. 또한, C. riparius를 산란 직후부터 DEHP에 노출시킨 경우에는 성체 출현률, 암수 비율, 산란률에서는 용량-반응 관계를 가진 변화가 발견되지 않았으나, 산란된 알의 부화율은 DEHP에 노출된 경우 유의하게 감소하는 것이 관찰되었다. 이러한 결과를 종합하여 볼 때. DEHP는 O. latpes와 C. riparius 모두 생식 작용에 영향을 미치며, 그 작용 기작은 일반적으로 발견되는 에스트로젠(estrogen) 활성이 아닌 암놈의 생식기관의 발달을 직, 간접적으로 저해함으로서 정상적인 알의 생성을 방해하는 이른바 항-에스트로젠 기작을 보이는 것으로 추정된다. 본 연구에서는 DEHP 위해성 평가를 위한 기본 자료로서, 생식작용 영향에 대한 새로운 자료를 제시하였다.

• Journal of Microbiology and Biotechnology
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• 제33권10호
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• pp.1351-1360
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• 2023

Endocrine-disrupting chemicals (EDCs) are compounds that disturb hormonal homeostasis by binding to receptors. EDCs are metabolized through hepatic enzymes, causing altered transcriptional activities of hormone receptors, and thus necessitating the exploration of the potential endocrine-disrupting activities of EDC-derived metabolites. Accordingly, we have developed an integrative workflow for evaluating the post-metabolic activity of potential hazardous compounds. The system facilitates the identification of metabolites that exert hormonal disruption through the integrative application of an MS/MS similarity network and predictive biotransformation based on known hepatic enzymatic reactions. As proof-of-concept, the transcriptional activities of 13 chemicals were evaluated by applying the in vitro metabolic module (S9 fraction). Identified among the tested chemicals were three thyroid hormone receptor (THR) agonistic compounds that showed increased transcriptional activities after phase I+II reactions (T3, 309.1 ± 17.3%; DITPA, 30.7 ± 1.8%; GC-1, 160.6 ± 8.6% to the corresponding parents). The metabolic profiles of these three compounds showed common biotransformation patterns, particularly in the phase II reactions (glucuronide conjugation, sulfation, GSH conjugation, and amino acid conjugation). Data-dependent exploration based on molecular network analysis of T3 profiles revealed that lipids and lipid-like molecules were the most enriched biotransformants. The subsequent subnetwork analysis proposed 14 additional features, including T4 in addition to 9 metabolized compounds that were annotated by prediction system based on possible hepatic enzymatic reaction. The other 10 THR agonistic negative compounds showed unique biotransformation patterns according to structural commonality, which corresponded to previous in vivo studies. Our evaluation system demonstrated highly predictive and accurate performance in determining the potential thyroid-disrupting activity of EDC-derived metabolites and for proposing novel biotransformants.