Jin Yuanxiang, Chen Guanliang, Fu Zhengwei
Department of Biotechnology, College of Biological and Environmental Engineering, Zhejiang University of Technology, Zhejiang, Hangzhou, 310032, China.
Environ Toxicol. 2016 Oct;31(10):1276-86. doi: 10.1002/tox.22137. Epub 2015 Mar 24.
The flame retardant tris (2-butoxyethyl) phosphate (TBEP) is a frequently detected contaminant in the environment. In the cultured TM3 cells (originated from ATCC), effects of TBEP on the induction of oxidative stress and endocrine disruption were evaluated. It was observed that exposure to 100 μg/mL TBEP for 24 h significantly reduced the viability of TM3 cells. The mRNA levels of genes related to oxidative stress including Sod, Gpx1, Cat, and Gsta1 were changed in a dose-dependent and/or time-dependent manner after exposure to 30 and 100 μg/mL TBEP for 6, 12, or 24 h. Moreover, notable decrease in glutathione (GSH) contents and increases in oxidized glutathione (GSSG) contents as well as the antioxidant enzyme activities like superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase were found in the group treated with 100 μg/mL TBEP for 24 h, indicating that TBEP induced oxidative stress in TM3 Leydig cells. In addition, the expression of genes related to testosterone (T) synthesis including cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), cytochrome P450 17α-hydroxysteroid dehydrogenase (P450-17α), and 17β-hydroxysteroid dehydrogenase (17β-HSD) and T levels in medium were remarkably declined by the treatment of 100 μg/mL TBEP for 24 h. And TBEP could inhibit the expression of P450-17α and 17β-HSD and T levels up-regulated by hCG in TM3 cells. Taken together, these findings indicated that TBEP can induce oxidative stress and alter steroidogenesis in TM3 cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1276-1286, 2016.
阻燃剂磷酸三（2-丁氧基乙基）酯（TBEP）是环境中经常检测到的污染物。在培养的TM3细胞（源自美国典型培养物保藏中心）中，评估了TBEP对氧化应激诱导和内分泌干扰的影响。观察到，暴露于100μg/mL TBEP 24小时会显著降低TM3细胞的活力。在暴露于30和100μg/mL TBEP 6、12或24小时后，与氧化应激相关的基因Sod、Gpx1、Cat和Gsta1的mRNA水平呈剂量依赖性和/或时间依赖性变化。此外，在100μg/mL TBEP处理24小时的组中，发现谷胱甘肽（GSH）含量显著降低，氧化型谷胱甘肽（GSSG）含量增加，以及超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽S-转移酶等抗氧化酶活性增加，表明TBEP在TM3睾丸间质细胞中诱导了氧化应激。此外，在100μg/mL TBEP处理24小时后，与睾酮（T）合成相关的基因细胞色素P450胆固醇侧链裂解酶（P450scc）、细胞色素P450 17α-羟类固醇脱氢酶（P450-17α）和17β-羟类固醇脱氢酶（17β-HSD）的表达以及培养基中的T水平显著下降。并且TBEP可以抑制TM3细胞中P450-17α和17β-HSD的表达以及hCG上调的T水平。综上所述，这些发现表明TBEP可以诱导氧化应激并改变TM3细胞中的类固醇生成。©2015威利期刊公司。环境毒理学31:1276 - 1286，2016。
