Örebro Life Science Center, Academy of Science, Technology, Örebro University, Örebro, Sweden.
Environ Toxicol Chem. 2014 Apr;33(4):891-9. doi: 10.1002/etc.2509. Epub 2014 Mar 3.
The incorporation of brominated flame retardants into industrial and household appliances has increased their occurrence in the environment, resulting in deleterious effects on wildlife. With the increasing restraints on available compounds, there has been a shift to using brominated flame retardants that has seen the production of alternative brominated flame retardants such as 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH), which has been detected in the environment. In previous in silico and in vitro studies the authors have shown that TBECH can activate both the human androgen receptor (hAR) and the zebrafish AR (zAR) suggesting that it is a potential endocrine disruptor. The present study was aimed at determining the interaction of TBECH with the chicken AR (cAR). In the present study, TBECH bound to cAR, but in vitro activation assay studies using the chicken LMH cell line showed it had a potency of only 15% compared with testosterone. Sequence difference between ARs from different species may contribute to the different responses to TBECH. Further quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis showed that TBECH interacted with and altered the expression of both thyroid receptors and estrogen receptors. In addition, the qRT-PCR analysis showed that TBECH altered the transcription pattern of genes involved in inflammatory, apoptotic, proliferative, DNA methylation, and drug-metabolizing pathways. This demonstrates that TBECH, apart from activating cAR, can also influence multiple biological pathways in the chicken.
工业和家用电器中溴系阻燃剂的加入增加了它们在环境中的出现，对野生动物产生了有害影响。随着可用化合物的限制越来越多，已经转向使用溴系阻燃剂，这导致了替代溴系阻燃剂的生产，如 1,2-二溴-4-(1,2-二溴乙基)环己烷（TBECH），已经在环境中检测到。在以前的计算机模拟和体外研究中，作者已经表明 TBECH 可以激活人类雄激素受体（hAR）和斑马鱼 AR（zAR），这表明它是一种潜在的内分泌干扰物。本研究旨在确定 TBECH 与鸡 AR（cAR）的相互作用。在本研究中，TBECH 与 cAR 结合，但使用鸡 LMH 细胞系的体外激活测定研究表明，它的效力仅为睾酮的 15%。不同物种 AR 之间的序列差异可能导致对 TBECH 的不同反应。进一步的定量逆转录聚合酶链反应（qRT-PCR）分析表明，TBECH 相互作用并改变了甲状腺受体和雌激素受体的表达。此外，qRT-PCR 分析表明，TBECH 改变了参与炎症、凋亡、增殖、DNA 甲基化和药物代谢途径的基因的转录模式。这表明，除了激活 cAR 之外，TBECH 还可以影响鸡的多个生物学途径。
