本文選題：雌激素類化合物 + 沉積物有機提取物��； 參考：《上海大學》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的生殖及發(fā)育毒性，成為環(huán)境毒理學領域的關注熱點之一。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，受到人們的關注，但關于它們的聯(lián)合毒性效應及作用機制仍需加強研究。 本文運用經(jīng)典的人類乳腺癌細胞MCF-7增殖實驗，采用CCK8法測試了典型雌激素類化合物對MCF-7細胞增殖的單一毒性及不同實驗設計下的聯(lián)合毒性效應；并從雌激素受體和細胞內(nèi)活性氧水平變化方面探討了雌激素干擾物對MCF-7細胞增殖毒性作用途徑；同時進行了黃浦江和蘇州河沉積物有機提取物對MCF-7細胞增殖的復合毒性效應及對細胞內(nèi)ROS水平的影響，主要結(jié)果如下： （1）E2、EV、DES、BPA促進了人類乳腺癌細胞MCF-7的增殖，而DEHP、MEHP對MCF-7細胞增殖沒有影響；析因?qū)嶒灪偷葷舛扰浔葍煞N實驗設計研究DES和EV的二元混合物對MCF-7細胞的增殖效應均表現(xiàn)為加和效應或接近加和效應。 （2）目標化合物E2、DES、BPA對MCF-7細胞的ER受體蛋白有一個明顯的表達，說明它們可能是通過雌激素受體（ER）調(diào)節(jié)機制對MCF-7細胞增殖產(chǎn)生促進作用的。此外E2、EV和BPA都可調(diào)節(jié)MCF-7細胞內(nèi)ROS水平，，他們在誘導氧化應激的同時，又發(fā)揮著抗氧化性機制，使細胞內(nèi)氧化還原水平處于動態(tài)平衡中；DES和DEHP對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作用時對細胞內(nèi)ROS水平的影響。 （3）黃浦江和蘇州河沉積物的有機提取物對MCF-7細胞增殖的毒性測試結(jié)果顯示，除個別點外，大部分樣點均表現(xiàn)出不同程度的MCF-7細胞增殖的毒性效應，且呈劑量-效應依賴和時間-效應依賴關系。并對MCF-7細胞內(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污染物的污染，并且部分河段污染較嚴重，但具體是受到哪類污染物污染需要進一步進行化學分析確認。
[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.
【學位授予單位】：上海大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R114;X503.1

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