• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.176.2-177
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• 2001

• Environmental Analysis Health and Toxicology
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• 제22권4호
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• pp.321-327
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• 2007

4-nonylphenol (4-NP)이 해산어류인 조피볼락, Sebastes schlegeli의 혈장 vitellogenin (VTG), alkaline-labile protein phosphorus (ALPP), calcium(Ca), glutamate pyruvate transaminase (GPT) 및 hepatosomatic index (HSI)에 미치는 영향을 조사하였다. 실험어에 3일간격으로 $estradiol-17{\beta}$ ($E_2$, 5 mg/kg B.W.) 또는 4-NP(0, 10, 50, 100및 200 mg/kg B.W.)을 복강에 2번 주사한 후, 7일째에 채혈과 적출을 통해 혈장과 간장을 수집해 분석이 실시되었다. 대조 실험어에는 용매로 사용된 70% 에탄올만이 투여되었다. $E_2$ 투여 실험어의 혈장 단백질을 전기 영동상으로 분석한 결과 약 170 kDa의 위치에서 짙은 VTG 밴드가 관찰되었으나, 용매만 투여한 대조 실험어의 혈장에서는 동일 밴드가 관찰되지 않았다. 4-NP 투여한 모든 실험어의 혈장 단백질에서는 $E_2$ 투여 실험어와 동일한 VTG 밴드가 관찰되었다. 혈장 ALPP와 Ca 농도도 4-NP 투여 실험어에서 $E_2$ 투여 실험어와 유사하게 증가하였으며, 이들 농도 변화는 VTG 합성과 더불어 증가하는 경향을 나타냈다. 혈장 전위효소인 GPT와 HSI도 $E_2$ 투여 실험어와 유사하게 4-NP가 투여된 모든 실험어에서 급격히 증가하였다. 이상의 결과로부터 연안생태계 내에서 서식하는 어류가 4-NP과 같은 내분비 장애물질(Endocrine Disrupting compounds, EDCs)에 의해 영향을 받는지를 규명하기 위한 생물학적 지표로서 VTG와 더불어 혈장 ALPP와 Ca이 사용가능 할 것으로 판단된다. 또한, 조피볼락과 같은 해산어가 EDCs에 노출되어 VTG가 합성될 때 간장 기능의 손상으로 혈장 전위효소인 GPT가 일시적으로 종가하고 간장도 비대해져 HSI가 높아지는 것으로 판단된다.

• Environmental Analysis Health and Toxicology
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• 제20권3호
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• pp.195-203
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• 2005

Cytochrome P45O 17$\alpha$-hydroxylase (CYPI 7) and cytorhrome P45O aromata.ie (CYPI 9) are key steroidogenic enzymes in androgen and estrogen synthesis. ThiL study evaluated the effects of nonylphenol (NP) on CYP17 and CYP19 expression in the ovary of Sprague-Dawley rats. All female rats were administered orally with the vehicle (control, corn oil), diethylstilbestrol (DES, 5.0 $\mu$g/kg) and NP (50, 100, or 200 mg/kg/day), which was startinB when they were weaned at 21 days of age for 20 days. Twenty four hours after final dose, the animals were anelthetized with ether. Significant decreases in the uterus (wet weight) were observed with 5.0 $\mu$g/kg/day DES (78$\%$, of control) and 200 mg/kg/day NP (62$\%$ of control), respectively Additionally, ovarian weight was significantly decreased with 5.0 $\mu$g/kg/day DES (63$\%$ of control) and 200 mg/kg/day NP (72$\%$ of control). The serum estradiol levels were sligHtly lower in DES and high dose NP treatment groups, but the 74 levels were not affected by DES and NP. The expression of the ovarian CYP19 gene increased with low doses (50 and 100 mg/kg/day) of NP. while DES and high dose oi NP (200 mg/kg/day) did not affect on the CYP19 mRNA levels. In contrast to the CYP19 gene, the CYP17 gene expreLsion level was significantly down-regulated by the DES and 200 mg/ks/day NP. This result suggestE that NP inhibits ovarian estrogen synthelis by supprelsing CYP17 mRNA efprelsion, And different mechanisml might exist for the expression of Lteroidogenic CYP17 and CYP19 genes in the ovary of Sprague-Dawley rats in response to NP.

• Fisheries and Aquatic Sciences
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• 제12권4호
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• pp.293-298
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• 2009

Several studies have reported that nonylphenol (NP) and 2,2', 4,6,6'-pentachlorobiphenyl (PCB104) exhibit estrogenic activity. To investigate the estrogenic potency of NP and PCB104 during oocyte maturation, fully vitellogenic oocytes (0.76 mm diameter in average) of yellow fin goby, Acanthogobius flavimanus, were exposed in vitro to these chemicals at different concentrations (0.1, 1, 10, 100, and 1,000 ng/mL) with the exogenous precursor $17\alpha$-hydroxyprogesterone ($17{\alpha}OHP$) 50 ng/mL in the presence or absence of human chorionic gonadotropin (HCG). The production of testosterone (T), estradiol-$17\beta$ (E2), and $17\alpha,20\beta$-dihydroxy-4-pregnen-3-one ($17\alpha20{\beta}OHP$) in response to NP or PCB104 were measured by radioimmunoassay. Steroid levels were also expressed as E2/T and E2/$17\alpha20{\beta}OHP$ ratios. In the absence of HCG, no significant differences in either NP or PCB104 treatment groups were observed. In the presence of HCG, NP treatment did not show significant differences in the production of T, E2, and $17\alpha20{\beta}OHP$ at any concentrations tested, but E2/T ratios were decreased at concentrations of 0.1, 1, 10, and 1,000 ng/mL compared with the control group. PCB104 decreased E2 production at concentrations of 0.1, 10, and 1000 ng/mL, but did not show significant differences in the production of T and $17\alpha20{\beta}OHP$ at any concentration tested. While E2/T ratios were decreased at PCB104 concentrations of 0.1, 1, 10, and 1,000 ng/mL, E2/$17\alpha20{\beta}OHP$ ratios were also decreased at 0.1, 10, and 1,000 ng/mL compared with the control. Results indicate that both NP and PCB104 appeared to have antiestrogenic effects during this phase.

• 분석과학
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• 제17권3호
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• pp.263-270
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• 2004

알킬페놀에톡실레이트 (APEO)는 주로 비이온성 계면활성제로 쓰이고 있으며 세제, 액체연료 및 농약에도 이용이 되고 있다. APEO 자체는 독성물질로 분류되어 있지 않지만, 그 대사생성물질인 단사슬 APEO, 알킬페놀 및 카르복실 유도체등은 폐수 또는 음용수를 염소처리하는 동안 mutagenic ring halogenated derivative를 생성한다. 이들 생성물들은 estrogenic effect를 나타내기 때문에 APEO를 제한 또는 규제하고 있는 추세이다. 본 연구에서는 APEO의 대사체로서 단사슬 APEO 인 4-nonylphenol-di-ethoxylate (NP2EO), 4-octylphenol-di-ethoxylate (OP2EO)를 분석하기 위해서 p-n-nonylphenol-di-ethoxylate-ring-$^{13}C_6$을 내부표준물질로 사용하여 HPLC/ESI/MS를 이용하여 분석하였다. 분석조건은 이온화 용매인 trifluoroacetic acid가 $10{\mu}M$이 되도록 각각 물과 메탄올에 첨가시켜 사용하였다. 물시료 1 L에 진한 황산을 이용하여 pH를 2이하로 조정한 후, 아세톤, 메탄올 및 물 (pH 2)로 활성화시킨 Sep-Pak $C_{18}$에 loading 시킨 후 아세톤으로 용출하여 시료용액으로 하였다. 이 방법으로 농도범위가 20 ~ 500 ng/L 내에서 검량선의 직선성은 r=0.999 (OP2EO)와 0.990 (NP2EO)였으며, 검출한계는 OP2EO는 20 ng/L, NP2EO는 50 ng/L 이었다. 정확도 및 정밀도는 85.8~122.1% 및 8.2~18.8 %로 좋은 결과를 나타냈다. 이 방법은 환경시료로부터 미량의 APEO를 분석하는데 사용될 수 있고, APEO 오염실태 조사에 응용될 수 있을 것으로 사료된다.

• 한국발생생물학회지:발생과생식
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• 제16권1호
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• pp.9-18
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• 2012

The effects of the estrogenic compound 4-nonylphenol (4-NP) on vitellogenesis in juvenile olive flounder ($Paralichthys$ $olivaceus$) and rockfish ($Sebastes$ $schlegeli$) exposed continuously at 10, 50 and $100{\mu}g{\ell}^{-1}$ levels for 7 days were compared. The expression of VTG mRNA level and protein using specific probes were examined. The levels of plasma estradiol-17 ${\beta}(E_2)$ and testosterone (T) were assessed by radioimmunoassay (RIA). Plasma $E_2$ concentrations increased significantly in two female fish species exposed to $100{\mu}g{\ell}^{-1}$ of 4-NP over concentrations in control fish. Plasma T concentrations increased in $P.$ $olivaceus$. Four days after exposure, the level of VTG mRNA expression increased in $P.$ $olivaceus$ and $S.$ $schlegeli$ exposed to $20{\mu}g{\ell}^{-1}$ of 4-NP. In addition, plasma VTG protein expression was seen in $P.$ $olivaceus$ and $S.$ $schlegeli$. In $S.$ $schlegeli$ and $P.$ $olivaceus$ exposed to 4-NP, the changes were noticed mainly in hepatocytic vaculation after 7 days of exposure. Thus, 4-NP may disrupt vitellogenesis in immature fish both directly and indirectly via disrupted steroidogenesis and liver pathology. Immature $S.$ $schlegeli$ were the most sensitive to 4-NP exposure in vitellogenesis.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2004년도 제4회 발생공학 국제심포지움 및 학술대회
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• pp.43-44
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• 2004

• Environmental Analysis Health and Toxicology
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• 제22권3호
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• pp.235-245
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• 2007

Toxicity of nonlyphenol (NP) one of EDCs was studied with focus on reproduction of the crucian carp, Carassius auratus. Fishes were cultured under control and nonylphnol exposure conditions for 32 weeks. Experimental group was composed of total of 4 groups, 1 control condition and 3 nonylphenol exposure condition ($18\;{\mu}g\;NP\;L^{-1},\;37\;{\mu}g\;NP\;L^{-1}\;and\;83\;{\mu}g\;NP\;L^{-1}$). Survival rate was found to be similar in control and $18\;{\mu};NP\;L^{-1}$. However, it is lower In the $37\;{\mu};NP\;L^{-1}$ and $83\;{\mu};NP\;L^{-1}$ in comparison to the control group. Deformation of gonads was the highest in the exposure condition of $18{\mu};NP\;L^{-1}$ with the female illustrating higher ratio than the male. GSI was not much different in the male but in the female, NP exposure group illustrated lower value compared to the control group. HSI and GI did not illustrate any clear differences between the control and exposure group for both male and female. Intersex was 0% in the wild group, 4.16% in the laboratory control group, and 25.67% in the NP exposure condition with female illustrating higher compared to male. Concentration of blood vitellogenin in female illustrated no clear differences between the control and NP exposure group. However, in the male, it was higher in the NP exposure group in comparison to the control group, and illustrated higher values of vitellogenin compared to the figures found in the female of same con-centration condition.

• 한국발생생물학회지:발생과생식
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• 제22권4호
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• pp.379-391
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• 2018

Through the development of organic synthetic skill, chemicals that mimic signaling mediators such as steroid hormones have been exposed to the environment. Recently, it has become apparent that this circumstance should be further studied in the field of physiology. Estrogenic action of chronic low-dose nonylphenol (NP) and di-(2-ethylhexyl) phthalate (DEHP) in mouse uterus was assessed in this study. Ten to twelve-week-old female mice (CD-1) were fed drinking water containing NP (50 or $500{\mu}g/L$) or DEHP (133 or $1,330{\mu}g/L$) for 10 weeks. Uterine diameter, the thickness of myometrium and endometrium, and the height of luminal epithelial cells were measured and the number of glands were counted. The expression levels of the known $17{\beta}$-estradiol ($E_2$)-regulated genes were evaluated with real-time RT-PCR methodology. The ration of uterine weight to body weight increased in $133{\mu}g/L$ DEHP. Endometrial and myometrial thickness increased in 133 and $1,330{\mu}g/L$ DEHP treated groups, and in 50, $500{\mu}g/L$ NP and $133{\mu}g/L$ DEHP, respectively. The height of luminal epithelial cell decreased in NP groups. The numbers of luminal epithelial gland were decreased in NP groups but increased in $50{\mu}g/L$ DEHP group. The histological characters of glands were not different between groups. The mRNA expression profiles of the known $17{\beta}$-estradiol ($E_2$) downstream genes, Esr1, Esr2, Pgr, Lox, and Muc1, were also different between NP and DEHP groups. The expression levels dramatically increased in some genes by the NP or DEHP. Based on these results, it is suggested that the chronic low-dose NP or DEHP works as estrogen-like messengers in uterus with their own specific gene expression-regulation patterns.

• Environmental Analysis Health and Toxicology
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• 제18권4호
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• pp.271-276
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• 2003

The purpose of the present study was to perform experiments of cytotoxicity using HeLa cell and to evaluate the possibility that QSAR is applicable to the cytotoxicity of alkylphenols. Higher toxicities were found in four alkylphenols in the following order: 4-n-Nonylphenol) 4-tert-Octylphenol) 4-n-Octylphenol > 4-n Heptylpheonl. Whereas other alkylphenols were apparently less toxic. By using Percent Hydrophilic Surface Area (PHSA) quantitative structure-activity relationships (QSARs) models were developed: Cytotoxicity (%) = 90.14089-4.72224 PHSA ($R^2$=0.2046, $\alpha$=0.0265). It is concluded that some of the obtained data are useful to determine whether QSAR methods can be of general use in predicting that until further work is undertaken to develop QSARs for a much wider range of homologous series of alkylphenol compounds.