天堂国产午夜亚洲专区-少妇人妻综合久久蜜臀-国产成人户外露出视频在线-国产91传媒一区二区三区

典型環(huán)境內(nèi)分泌干擾物對(duì)MCF-7細(xì)胞的增殖毒性及初步機(jī)理探討

發(fā)布時(shí)間:2018-06-23 03:31

  本文選題:雌激素類化合物 + 沉積物有機(jī)提取物; 參考:《上海大學(xué)》2013年碩士論文


【摘要】:雌激素類化合物是典型的環(huán)境內(nèi)分泌干擾物(environmental endocrinedisrupting chemicals, EDCs),在低劑量下就具有較強(qiáng)的生殖及發(fā)育毒性,成為環(huán)境毒理學(xué)領(lǐng)域的關(guān)注熱點(diǎn)之一。其中雌二醇(E2)、戊酸雌二醇(EV)、己烯雌酚(DES)、雙酚A(BPA)、DEHP及其代謝產(chǎn)物MEHP被認(rèn)為是典型雌激素類化合物,在水環(huán)境中廣泛存在,受到人們的關(guān)注,但關(guān)于它們的聯(lián)合毒性效應(yīng)及作用機(jī)制仍需加強(qiáng)研究。 本文運(yùn)用經(jīng)典的人類乳腺癌細(xì)胞MCF-7增殖實(shí)驗(yàn),采用CCK8法測(cè)試了典型雌激素類化合物對(duì)MCF-7細(xì)胞增殖的單一毒性及不同實(shí)驗(yàn)設(shè)計(jì)下的聯(lián)合毒性效應(yīng);并從雌激素受體和細(xì)胞內(nèi)活性氧水平變化方面探討了雌激素干擾物對(duì)MCF-7細(xì)胞增殖毒性作用途徑;同時(shí)進(jìn)行了黃浦江和蘇州河沉積物有機(jī)提取物對(duì)MCF-7細(xì)胞增殖的復(fù)合毒性效應(yīng)及對(duì)細(xì)胞內(nèi)ROS水平的影響,主要結(jié)果如下: (1)E2、EV、DES、BPA促進(jìn)了人類乳腺癌細(xì)胞MCF-7的增殖,而DEHP、MEHP對(duì)MCF-7細(xì)胞增殖沒有影響;析因?qū)嶒?yàn)和等濃度配比兩種實(shí)驗(yàn)設(shè)計(jì)研究DES和EV的二元混合物對(duì)MCF-7細(xì)胞的增殖效應(yīng)均表現(xiàn)為加和效應(yīng)或接近加和效應(yīng)。 (2)目標(biāo)化合物E2、DES、BPA對(duì)MCF-7細(xì)胞的ER受體蛋白有一個(gè)明顯的表達(dá),說明它們可能是通過雌激素受體(ER)調(diào)節(jié)機(jī)制對(duì)MCF-7細(xì)胞增殖產(chǎn)生促進(jìn)作用的。此外E2、EV和BPA都可調(diào)節(jié)MCF-7細(xì)胞內(nèi)ROS水平,,他們?cè)谡T導(dǎo)氧化應(yīng)激的同時(shí),又發(fā)揮著抗氧化性機(jī)制,使細(xì)胞內(nèi)氧化還原水平處于動(dòng)態(tài)平衡中;DES和DEHP對(duì)ROS水平影響不明顯;DES、BPA、DEHP與EV聯(lián)合作用沒有改變這三種化合物單獨(dú)作用時(shí)對(duì)細(xì)胞內(nèi)ROS水平的影響。 (3)黃浦江和蘇州河沉積物的有機(jī)提取物對(duì)MCF-7細(xì)胞增殖的毒性測(cè)試結(jié)果顯示,除個(gè)別點(diǎn)外,大部分樣點(diǎn)均表現(xiàn)出不同程度的MCF-7細(xì)胞增殖的毒性效應(yīng),且呈劑量-效應(yīng)依賴和時(shí)間-效應(yīng)依賴關(guān)系。并對(duì)MCF-7細(xì)胞內(nèi)ROS水平產(chǎn)生一定的影響。說明黃浦江、蘇州河沉積物受到了有機(jī)污染物的污染,并且部分河段污染較嚴(yán)重,但具體是受到哪類污染物污染需要進(jìn)一步進(jìn)行化學(xué)分析確認(rèn)。
[Abstract]:Estrogen compounds are typical environmental endocrine disruptors (environmental endocrinedisrupting chemicals,), which have strong reproductive and developmental toxicity at low doses, and have become one of the focuses in the field of environmental toxicology. Among them, estradiol (E2), estradiol valerate (EV), diethylstilbestrol (des), bisphenol A (BPA) DEHP and its metabolite MEHP are considered to be typical estrogen compounds, which are widely existed in water environment and have attracted people's attention. However, the study of their joint toxicity and its mechanism need to be strengthened. In this paper, the single toxicity of typical estrogen compounds to MCF-7 cell proliferation and the combined toxicity under different experimental designs were tested by CCK8 method using the classical human breast cancer cell MCF-7 proliferation test. The toxic effects of estrogen disruptors on MCF-7 cell proliferation were also discussed from the aspects of estrogen receptor and intracellular reactive oxygen species (Ros) levels. At the same time, the compound toxic effects of organic extracts from sediments from Huangpu River and Suzhou River on the proliferation of MCF-7 cells and their effects on intracellular Ros levels were studied. The main results were as follows: (1) E2EVV DESPA promoted the proliferation of human breast cancer cell line MCF-7. The proliferation of MCF-7 cells was not affected by DEHP- MEHP. The effects of des and EV binary mixtures on the proliferation of MCF-7 cells were studied by factorial experiment and equal concentration ratio. (2) the ER response of the target compound E2DSE BPA to MCF-7 cells was either additive effect or near additive effect. (2) the ER response of the target compound E2DSE BPA to MCF-7 cells was studied. Body protein has an obvious expression. These results suggest that they may promote the proliferation of MCF-7 cells through estrogen receptor (ER) regulation. In addition, both E2EV and BPA could regulate the Ros level in MCF-7 cells. They not only induced oxidative stress, but also played an antioxidant mechanism, so that the intracellular redox level was in a dynamic balance. The effects of des and DEHP on Ros levels were not obvious. The combined action of DESPA-DEHP and EV did not change the effect of these three compounds on intracellular Ros levels. (3) the toxicity test of organic extracts from sediments of Huangpu River and Suzhou River to MCF-7 cell proliferation showed that, except for a few points, Most of the samples showed toxic effects of MCF-7 cell proliferation to varying degrees, and showed dose-effect and time-effect dependence. The Ros level in MCF-7 cells was also affected to some extent. The results show that the sediments of Huangpu River and Suzhou River are polluted by organic pollutants, and some of them are polluted seriously, but it is necessary to make chemical analysis to confirm which kinds of pollutants are polluted.
【學(xué)位授予單位】:上海大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2013
【分類號(hào)】:R114;X503.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 蘇永紅;唐柱云;曾科;;重金屬聯(lián)合毒性研究進(jìn)展[J];現(xiàn)代農(nóng)業(yè)科技;2007年10期

2 蘇麗敏;劉惠清;李志群;田竹君;呂軍;趙峰;朱曉琳;;三種農(nóng)藥與三種重金屬對(duì)發(fā)光菌的聯(lián)合毒性效應(yīng)[J];東北師大學(xué)報(bào)(自然科學(xué)版);2011年04期

3 陸繼龍;郝立波;王春珍;李巍;白榮杰;閻冬;;第二松花江中下游水體鄰苯二甲酸酯分布特征[J];環(huán)境科學(xué)與技術(shù);2007年12期

4 曾鳴;林志芬;尹大強(qiáng);殷克東;;混合污染物聯(lián)合毒性研究進(jìn)展[J];環(huán)境科學(xué)與技術(shù);2009年02期

5 李康;戎志毅;賈麗娟;殷浩文;;蘇州河沉積物中的PCDD/Fs研究[J];環(huán)境科學(xué)與技術(shù);2009年09期

6 魏榮菲;莊舜堯;楊浩;戎靜;王小雷;;蘇州河網(wǎng)區(qū)河道沉積物重金屬的污染特征[J];湖泊科學(xué);2010年04期

7 徐菁;朱從麗;王喬;宋健;;血管平滑肌細(xì)胞的體外氧化應(yīng)激反應(yīng)及雌激素的影響[J];中國(guó)組織化學(xué)與細(xì)胞化學(xué)雜志;2010年06期

8 張蕾,徐鏡波,楊麗;析因試驗(yàn)設(shè)計(jì)在環(huán)境污染物聯(lián)合毒性研究中的應(yīng)用[J];干旱環(huán)境監(jiān)測(cè);2004年01期

9 雷少波;唐羅生;朱曉華;段宣初;;雌激素對(duì)藍(lán)光及過氧化氫誘導(dǎo)的ARPE-19細(xì)胞內(nèi)活性氧生成的影響[J];國(guó)際眼科雜志;2008年06期

10 李佳圓,欒榮生;環(huán)境內(nèi)分泌干擾物與人群健康的關(guān)系[J];國(guó)外醫(yī)學(xué)(衛(wèi)生學(xué)分冊(cè));2001年04期



本文編號(hào):2055563

資料下載
論文發(fā)表

本文鏈接:http://sikaile.net/yixuelunwen/yufangyixuelunwen/2055563.html


Copyright(c)文論論文網(wǎng)All Rights Reserved | 網(wǎng)站地圖 |

版權(quán)申明:資料由用戶1cb16***提供,本站僅收錄摘要或目錄,作者需要?jiǎng)h除請(qǐng)E-mail郵箱bigeng88@qq.com