Carcinogenesis, Teratogenesis & Mutagenesis ›› 2016, Vol. 28 ›› Issue (3): 161-168.doi: 10.3969/j.issn.1004-616x.2016.03.001

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Effects of 2, 2', 4, 4'-tetra polybrominated diphenyl ether on retinoid receptor and estrogen receptor

XIAO Yue1,2, ZHANG Jianqing2, JIANG Yousheng2, ZHOU Jian2, HUANG Haiyan2, WANG Xiaohui2, LI Shengnong2, LU Shaoyou2, LIN Xiaoshi2   

  1. 1. School of Public Health, Sichuan University, Chengdu 610041, Sichuan;
    2. Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, Guangdong, China
  • Received:2016-03-07 Revised:2016-04-21 Online:2016-05-31 Published:2016-05-31

Abstract: OBJECTIVE:To investigate effects and mechanisms of 2, 2', 4, 4'-tetra polybrominated diphenyl ether (BDE-47) on retinoid receptor (RXRα) and estrogen receptors (ERα, ERβ) in MCF-7 cells. METHODS:Stably expressed RXRα in MCF-7 cells at high and low levels were constructed via lentivirus transfection. After exposure of three transfected cell lines to polybrominated diphenyl (BDE-47), cell toxicity was analyzed using the Cell Counting Kit-8(CCK-8) assay. In addition, SOD vitality, MDA content and hOGG1 mRNA expression were analyzed using the TBA, XOD and RT-PCR assays, respectively. Expression levels in mRNA and protein for the three receptors (RXRα, ERα and ERβ) were determined by RT-PCR and Western blot respectively. RESULTS:BDE-47 induced significant cytotoxicity to MCF-7 cells. IC50 of BDE-47 to MCF-7 cells with normal, high and low expressions of RXRα were 23.15, 82.78 and 30.16 μmol/L, respectively. Highest toxicity was observed at 24 h after the exposure to BDE-47. Moreover, BDE-47 induced oxidative damage. Cells with high expression of RXRα receptor had increased toxicity tolerance against BDE-47-induced oxidative damage. BDE-47 also significantly inhibited the expression of RXRα in the three cell lines. For ER, BDE-47 exposure increased the expression of ERα and inhibited the expression of ERβ in normal and low RXRα expression cells, and vice versa in high RXRα expression cells. CONCLUSION:BDE-47 exposure significantly reduced the expression levels in mRNA and protein of RXRα. In addition, the exposure up-regulated ERα and down-regulated ERβ in normal and low RXRα cell lines, but showed opposite effects in the high RXRα cell line. Thus, interference of RXRα expression and breaking the balance of ERα and ERβ may be an important mechanism for disruption of neuroendocrine by BDE-47.

Key words: 2, 2', 4, 4'-tetrabromo diphenyl ether, retinoid X receptor, estrogen receptor, superoxide dismutase, malondialdehyde, human 8-hydroxy guanine DNA glycosidase

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