【摘要】：四溴雙酚A(TBBPA)作為一種溴代阻燃劑被廣泛應(yīng)用于塑料、電子產(chǎn)品、建筑材料和紡織品中,目前在土壤、水體沉積物和大氣等環(huán)境介質(zhì),以及水生生物、野生動(dòng)物和人體血液、母乳樣品中都有檢出。目前有關(guān)TBBPA毒性研究的報(bào)道逐漸增多,對(duì)其肝腎毒性、免疫毒性、神經(jīng)毒性和內(nèi)分泌干擾效應(yīng)等有了初步認(rèn)識(shí),但有關(guān)其細(xì)胞毒性及其作用機(jī)制尚不完全清楚。 本研究通過(guò)HepG2細(xì)胞模型,研究TBBPA暴露后的細(xì)胞毒性和毒作用機(jī)制,結(jié)果表明：TBBPA可影響HepG2細(xì)胞形態(tài)；HepG2細(xì)胞存活率與TBBPA處理呈濃度-效應(yīng)關(guān)系和時(shí)間-效應(yīng)關(guān)系,其12、24和48h的IC50分別為33.82、27.36和17.73μM；12、24和48h TBBPA處理的HepG2細(xì)胞LDH漏出率與TBBPA有濃度-效應(yīng)關(guān)系；TBBPA處理導(dǎo)致HepG2細(xì)胞內(nèi)ROS過(guò)量生成、GSH含量和SOD活力下降；加入抗氧化劑Trolox共同作用后,與TBBPA單獨(dú)處理相比,HepG2細(xì)胞內(nèi)ROS生成下降、GSH含量和SOD活力升高；在高劑量(30μM) TBBPA中加入抗氧化劑Trolox共同作用后,與TBBPA(30μM)單獨(dú)處理相比,HepG2細(xì)胞存活率顯著上升；20和30μMTBBPA處理均導(dǎo)致HepG2細(xì)胞線粒體膜電位下降和細(xì)胞凋亡率增加,但加入抗氧化劑Trolox共同作用后,其細(xì)胞凋亡情況無(wú)顯著性改變。 另外,本研究采用BMD法,選擇TBBPA染毒24h對(duì)HepG2細(xì)胞的抑制率為健康效應(yīng)靶點(diǎn),利用U.S.EPA開(kāi)發(fā)的BMDS2.2軟件,對(duì)其劑量-反應(yīng)關(guān)系進(jìn)行評(píng)估,結(jié)果表明其N(xiāo)OAEL、LOAEL、BMDL10和BMD10分別為10、15、9.45和10.34μM。 綜合本研究結(jié)果,可得出如下結(jié)論：(1) TBBPA暴露可導(dǎo)致HepG2細(xì)胞死亡：(2) TBBPA能誘導(dǎo)HepG2細(xì)胞產(chǎn)生氧化應(yīng)激；(3) TBBPA對(duì)HepG2細(xì)胞的毒性作用可能是通過(guò)氧化應(yīng)激產(chǎn)生的；(4) TBBPA能誘導(dǎo)HepG2細(xì)胞凋亡;(5) TBBPA染毒24h對(duì)HepG2細(xì)胞抑制率影響的BMDL10為9.45μM。
[Abstract]:Tetrabromobisphenol A (TBBPA) is widely used as a brominated flame retardant in plastics, electronics, building materials and textiles, and in environmental media such as soil, water, sediment and atmosphere, as well as aquatic organisms. Wild animals and human blood, breast milk samples have been detected. At present, there are more and more reports about the toxicity of TBBPA, and it has a preliminary understanding of its liver and kidney toxicity, immune toxicity, neurotoxicity and endocrine disrupting effect, but the cytotoxicity and its mechanism are not completely clear. In this study, HepG2 cell model was used to study the mechanism of cytotoxicity and toxicity after TBBPA exposure. The results showed that TBBPA could affect the morphology of HepG2 cells. There was a concentration-effect relationship between the survival rate of HepG2 cells and TBBPA treatment, and the LDH leakage rate of HepG2 cells treated with 1224 and 48h IC50 was 33.82 渭 M ~ 27.36 and 17.73 渭 M ~ (12) O ~ (24) and 48 h TBBPA, respectively. There was a concentration-effect relationship between LDH leakage rate and TBBPA. TBBPA treatment resulted in the excessive production of ROS, the decrease of GSH content and SOD activity in HepG2 cells, the decrease of ROS production and the increase of GSH content and SOD activity in HepG2 cells compared with TBBPA alone. Compared with TBBPA (30 渭 M) alone, the survival rate of HepG2 cells increased significantly after the addition of antioxidant Trolox in high dose (30 渭 M) TBBPA). Both 20 and 30 渭 MTBBPA treatment led to the decrease of mitochondrial membrane potential and the increase of apoptosis rate of HepG2 cells, but the apoptosis of HepG2 cells did not change after the addition of antioxidant Trolox. In addition, the BMD method was used to evaluate the dose-response relationship of HepG2 cells induced by TBBPA for 24 hours by using BMDS2.2 software developed by U.S.EPA. The results showed that the inhibition rate of HepG2 cells exposed to TBBPA for 24 hours was the target of health effect. BMDL10 and BMD10 were 100.159.45 and 10.34 渭 M. Based on the results of this study, the following conclusions can be drawn: (1) TBBPA exposure can lead to the death of HepG2 cells; (2) TBBPA can induce oxidative stress in HepG2 cells; (3) the toxic effect of TBBPA on HepG2 cells may be caused by oxidative stress; (4) TBBPA could induce apoptosis of HepG2 cells, (5) the inhibitory rate of HepG2 cells induced by TBBPA for 24 h was 9.45 渭 m.
【學(xué)位授予單位】：中國(guó)環(huán)境科學(xué)研究院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R114

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相關(guān)期刊論文 前10條

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本文編號(hào)：2304221