• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.168-168
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• 2002

To establish a test protocol for the rodent 20-day thyroid/pubertal assay, flutamide and diethylstilbestrol (DES) were administered to intact male Sprague-Dawley rats from postnatal day 33 for 20 days. Flutamide (1, 5, and 25 mg/kg/day) or DES (10, 20, and 40 ug/kg/day) was given once daily by oral gavage to immature male rats. Prepuce separation was significantly delayed in flutamide group and in DES group. One day after the last dose, the rats were killed and pituitary, thyroid, and reproductive organs were removed and weighed. Flutamide treatment resulted in a significant reduction in the weights of epididymides, ventral prostate, seminal vesicles plus coagulating glands and fluid (SVCGF), levator ani. bulbocarvenus muscles (LABC), Cowper's glands, and glans penis. The weight of adrenal glands decreased at % mg/kg/day, while testes and any other organ weights were unaffected. No microscopic changes were observed in the thyroid glands. Serum levels of testosterone wert significantly increased in the flutamide-treated groups and serum levels of estradiol were also increased. A significant reduction in the weights of testes, epididymides, ventral prostate, SVCGF, LABC, Cowpers glands, and glans penis of DES treated group. Serum testosterone and LH decreased significantly in DES group. Decrease of estradiol was observed, but not significant. These results indicate that flutamide and DES delay puberty in the male rat and its mode of action appears to be via altered secretion of steroids, which subsequently affect the development of the reproductive tract. (Supported by the grant from NITR/Korea FDA for Endocrine Disrupter Research.)

• Toxicological Research
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• 제18권1호
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• pp.59-64
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• 2002

Substantial evidences have been accumulated about the hormone-like effects of exogenous substances such as pesticides and industrial chemicals during past years. The effects of these substances on the endocrine system are believed to be either enhancing or reducing of various endocrine action. It is necessary to identify putative causal agents by the batter system and to assess their ability to disrupt the endocrine system. A variety of in vitro and In vivo approaches have been used to determine the androgenic effects of environmental chemicals. To establish the method for assessment of the putative endocrine disruptors with androgenic activity, we carried out the cell proliferation assay by MTS method after treatment with the various concentration of testosterone in LNCaP cells (human prostatic cancer cell line) and also observed the expression of androgen-related genes by quantitative RT-PCR. In the cell proliferation assay, the results showed that the grouth of LNCaP cells increased within level of at least 10pM testosterone. We measured by quantitative RT-PCR method on the effects of testosterone on mRNA expression of androgen receptor (AR), prostate-specific antigen (PSA), bone morphogenetic protein (BMP) and BMP receptor (BMPR) In LNCaP cells. The results demonstrated that mRNA expression of PSA and BMPR-IB was observed differently within level of at least 0.01 pM testosterone compared with non-treated control. These observations suggest that the detection of PSA and BMPR-IB mRNA by the quantitative RT-PCR in LNCaP cells is very sensitive method to identify the endocrine disruptors to have the androgenic effects.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.67-67
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• 2003

Tributyltin chloride (TBTCI) is an organotin compounds that have been widely used as antifouling agents and bioaccumulated in the food chain. TBTCI has been known to induce imposex in female gastropods. There are several reports that TBTCI increased testosterone level and inhibited the conversion of testosterone to estradiol by the aromatase cytochrome P450 enzyme. In this studies, we investigated the effects of TBTCI on steroidogenesis in testes, We dosed to 4-week-old Spragus-Dawleys (SD) male rats with TSTCI (0, 1, 5, 10, and 20mg/kg/day) daily by gavage for 14 days. TBTCI significantly decreased the weights of seminal vesicle, prostate, cowper's gland and LABC at 10 and 20mg/kg/day but significantly Increased the weights of liver at 10 and 20mg/kg/day and adrenals at 20mg/kg/day. mRNA levels of steroidogenic acute regulatory (StAR) and P450 aromatase were decreased and mRNA levels of cytochrome P450 17$\alpha$-hydroxylase/$C_{17-20}$ lyase (P450c17) were increased by TBTCI. TBTCI significantly increased serum testosterone level in dose-dependent manner. From above results, we found that TBTCI altered mRNA levels of enzymes related steroidogenesis, weights of organs and serum testosterone levels. This suggests that change of hormone levels may be due to alteration of mRNA levels of steroidogenic enzyme in testes, but further studies are necessary to investigate hormone levels in testis organ in order to find a relation of enzyme related to steroidogenesis with hormone levels. This work was supported by the Korea FDA Grant KFDA-03131-EDS-010.

• Toxicological Research
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• 제21권1호
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• pp.77-85
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• 2005

Cadmium is an environmental pollutant exposed from contaminated foods or cigarette smoking and known to cause oxidative damage in organs. We investigated the cadmium-induced apoptosis and cell arrest in human breast cancer cells, MCF-7 cells and MDA-MB-231 cells. Obvious apoptotic cell death was shown in CdCl₂ 100 μM treatment for 12 hr, which were determined by DAPI staining and flow cytometric analysis. In cell cycle analysis, MCF-7 cells and MDA-MB-231 cells were arrested in S phase and G2/M phase respectively. These could be explained by the induction of cell cycle inhibitory protein, p21/sup Waf1/Cip1/ and p27/sup Kip1/, expression and reduction of cyclin/Cdk complexes in both cell lines. The decreased expression of cyclin A and Cdk2 in MCF-7 cells and cyclin B1 and Cdc2 in MDA-MB-231 cells were consistent with the flow cytometric observation. p-ERK expression was increased dose-dependent manner in both cell lines. It suggests that ERK MAPK pathway are involved in cadmium-induced cell cycle arrest and apoptosis. Moreover, cotreatment of zinc (100 μM, 12 hr) recovered the cadmium-induced cell arrest in both cells, which shows cadmium-induced oxidative stress mediates apoptosis and cell cycle arrest in human breast cancer cells.

• 한국식품위생안전성학회지
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• 제14권4호
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• pp.408-414
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• 1999

자연계에 오염되어 있는 수많은 화학 물질들은 정상적인 내분비 기능을 교란한다. 내분비 교란 물질은 수계에 오염되면 야생동물과 사람에게 건강에 미치는 영향이 크다. 본 연구는 오염물질이 생체의 내분비계를 교란시키므로서 생성되는 난황 전구체 단백질로서 환경오염의 생물체의 지표로서 비트로게닌의 생성을 유도하는 내분비 교란 물질에 대하여 고찰하였다. 수계의 환경에서 서식하고 있는 물고기는 내분비계 교란 물질에 의하여 암컷에서는 번식률과 난백의 생산이 감소되고 수컷에서는 정소의 왜소화 및 암컷화로 유도되기도 한다. 여성호르몬 작용을 하는 화학물질에 노출된 수컷은 비트로게닌의 생성을 촉진하고, 암컷에 있어서 비트로게닌의 생성은 난백을 형성하는 동안 에스트로겐의 함량을 증가시켜 정상적인 활동을 제한하기도 한다. 따라서 수컷에서의 비트로게닌은 환경에 오염된 내분비교란 물질의 오염에 의하여 생성되게 된다. 결과적으로 수컷의 물고기에서 생성된 비트로게닌은 환경에 오염된 내분비 교란물질이 어느 정도 노출되어 있는가를 결정하는 생물학적 지표로 사용할 수 있다. 특히 치어의 경우 극미량의 내분비 교란물질에 노출되어도 믿을 만한 생물지표로서 이용될 수 있다.

• Clinical and Experimental Pediatrics
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• 제63권4호
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• pp.146-150
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• 2020

Background: The incidence of precocious puberty has increased throughout the 20th century. The association between precocious puberty and endocrine disrupting chemicals including agricultural pesticides has been a subject of global study, but human data are lacking. Purpose: We investigated the relationship between agricultural pesticides and the development of precocious puberty. Methods: We enrolled 60 female subjects at Severance Children's Hospital from December 2015 to January 2017. Of them, 30 were diagnosed with precocious puberty, while the other 30 prepubertal girls were enrolled as normal controls. We investigated their clinical characteristics and analyzed the urinary levels of 320 different agricultural pesticides. Results: Agricultural pesticide was detected in one of 30 patients with precocious puberty (3.3%) versus 2 of 30 girls in the normal control group (3.3% vs. 6.7%, P=0.554). Dinotefuran, a neonicotinoid-class insecticide, was detected in the samples of all 3 positive subjects. Conclusion: Our results showed no relationship between agricultural pesticides and the development of precocious puberty. Larger sample sizes and robustly controlled variables are necessary to further investigate this topic.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.119-123
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• 2016

Thyroid cancer, the most common endocrine neoplasia, consists of four main types of carcinomas: papillary, follicular, and anaplastic, all with thyroid follicular origin, and medullary thyroid cancer (MTC) related to para-follicular cells. Cronic diseases such as diverse cancers may be associated with cachexia, especially at advanced stage. Cancer-induced cachexia is associated with diminished quality of life, functional performance, reduced response to antitumor therapy, and increased morbidity and mortality. Myostatin (Mst) is one of the outstanding molecules in the skeletal muscle loss process in cancer and it may be released by both skeletal muscle and cachexia-inducing tumors. Recently changes in serum levels of Mst have been identified as an important factor of cancer-induced cachexia. The goal of this study was to assessserum Mst levels in MTC patients. In this descriptive and case-control study, 90 participants were selected, comprising 45 MTC patients (20 males, $29{\pm}13.9years$, 25 females, $29{\pm}14.5years$) and 45 control individuals (25 males, $23.1{\pm}11.6years$, 20 females, $31.5{\pm}14.4years$). Serum Mst was determined using an ELISA kit and body mass index (BMI) was calculated by weight and height measurements. The Kolmogorov Simonov test showed a normal distribution for log transformed Mst serum levels in both case and control groups. Geometric means were 5.9 and 8.2 ng/ml respectively, and a significant difference was found according to the independent t-test results (P<0.01). There was also a significant difference mean of Mst between females in control and MTC groups, but not for the males. Pearson correlation test showed no correlation between age and BMI with Mst serum levels. The findings of this study support the hypothesis that Mst serum levels may have a potential ability for early diagnosis of cachexia in MTC patients, especially in females.

• Preventive Nutrition and Food Science
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• 제21권2호
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• pp.104-109
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• 2016

In the current study, we investigated the longitudinal association between dietary acid load and the risk of insulin resistance (IR) in the Tehranian adult population. This longitudinal study was conducted on 925 participants, aged 22~80 years old, in the framework of the third (2006~2008) and fourth (2009~2011) phases of the Tehran Lipid and Glucose Study. At baseline, the dietary intake of subjects was assessed using a validated semi-quantitative food frequency questionnaire, and the potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores were calculated at baseline. Fasting serum insulin and glucose were measured at baseline and again after a 3-year of follow-up; IR was defined according to optimal cut-off values. Multiple logistic regression models were used to estimate the risk of IR according to the PRAL and NEAP quartile categories. Mean age and body mass index of the participants were 40.3 years old of $26.4kg/m^2$, respectively. Mean PRAL and NEAP scores were -11.2 and 35.6 mEq/d, respectively. After adjustment for potential confounders, compared to the lowest quartile of PRAL and NEAP, the highest quartile was accompanied with increased risk of IR [odds ratio (OR)=2.81, 95% confidence interval (CI)=1.32~5.97 and OR=2.18, 95% CI=1.03~4.61, respectively]. Our findings suggest that higher acidic dietary acid-base load, defined by higher PRAL and NEAP scores, may be a risk factor for the development of IR and related metabolic disorders.

• 환경생물
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• 제29권1호
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• pp.1-10
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• 2011

지구적으로 양서류가 감소하고 있다. 수정 후 변태에 이르는 생활사를 수중에서 진행하는 양서류는 수환경 내의 오염물질에 1차적으로 노출되며 독성효과에 대한 감수성이 높아 수환경의 오염에 특히 취약하다. 양서류는 수서생태계의 건강도 지표로서 유용할 뿐 아니라 배아 또는 유생에서 분자 및 개체수준의 다양한 생체지표를 이용한 내분비계장애물질을 비롯한 다양한 환경오염물질의 독성평가 모델로서도 유용하다. 양서류에서 얻어진 독성자료는 수환경 오염물질의 관리와 안전관리기준의 설정에 활발히 이용되고 있다. 다양한 알킬페놀류 화합물이 농업, 공업, 가정활동에 사용되고 있으며, 수환경 내에 잔류한다. 이들은 다양한 수생동물에서 내분비계장애 효과를 갖는 것으로 알려졌다. 본 소고에서는 양서류의 배아, 유생을 대상으로 알킬페놀류 화합물의 종류별, 노출경로 및 농도, 노출기간 및 발생단계 등에 따른 내분비계장애효과와 그 기작에 관한 국내외 자료를 정리하였다.

• Journal of Korean Neurosurgical Society
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• 제49권5호
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• pp.262-266
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• 2011

Objective : The endocrine dysfunction after the operation for suprasellar arachnoid cysts is not rare. The careful operation to prevent structures can prevent this complication, but it is not enough and effective to prevent it. Authors present technical surgical considerations to prevent this complication with a review of our suprasellar arachnoid cyst patients who had postoperative endocrine dysfunction. Methods : From January 2002 to December 2009, eight patients who had suprasellar arachnoid cysts with visual impairment underwent surgery. The mean age was 57.1 years (range, 33-77). Preoperatively, their endocrine function was clinically normal, and laboratory hormonal levels were within normal ranges. Cyst fenestration was performed by craniotomy (n=6) or by a neuro-endoscopic procedure (n=2), and, simultaneously, along with a cyst wall biopsy. Results : The surgery was uneventful in all eight patients, and there were no neurological morbidities. However, in four patients, endocrine dysfunction occurred postoperatively. We compared these four patients (group A) to the other 4 patients without endocrine dysfunction (group B) with intraoperative findings and with the histopathological findings of the cyst wall biopsy. The group A patients had more abundant vasculature on the cystic wall than the group B patients according to both the intraoperative findings and the histopathological findings. Conclusion : When performing a surgical cyst wall fenestration, surgeons should try to minimize the destruction of the cystic wall vasculature and not to make the fenestration at a site that contains many vascular striae.