Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Toxicol Lett. 2011 Feb 25;201(1):34-41. doi: 10.1016/j.toxlet.2010.12.002. Epub 2010 Dec 9.
Di-(2-ethylhexyl)-phthalate (DEHP) is the most widely used plasticizers in daily-life products. In this study we evaluated the influence of mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of DEHP, on the neurodevelopment in vitro. After neuronotypic PC12 cells were exposed to MEHP (0.25, 2.5, 25, and 250 μM), the effects of which on cell proliferation and differentiation were investigated. In undifferentiated PC12 cells, MEHP inhibited cell proliferation in a dose-dependent manner. After 24h of MEHP treatment, there was a dose-dependent G2/M cell cycle arrest as well as a sharp drop of DNA synthesis. During the process of NGF-induced differentiation of the cell line, 4 days of MEHP exposure (2.5-250 μM) increased membrane and cytoskeletal protein contents, enhanced NGF-induced neurite outgrowth, up-regulated the choline acetyl transferase (ChAT) mRNA and down-regulated tyrosine hydroxylase (TH) mRNA levels, which suggested the promoted differentiation towards the acetylcholine (ACh) phenotype at the expense of the dopamine (DA) phenotype. Take together, our results indicate that MEHP has a potential to disturb neurodevelopment by suppressing cell proliferation and promote cell differentiation in neurocytes.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是日常生活产品中最广泛使用的增塑剂。在这项研究中，我们评估了邻苯二甲酸单（2-乙基己基）酯（MEHP），DEHP 的活性代谢物，对体外神经发育的影响。在神经元型 PC12 细胞暴露于 MEHP（0.25、2.5、25 和 250 μM）后，研究了其对细胞增殖和分化的影响。在未分化的 PC12 细胞中，MEHP 呈剂量依赖性抑制细胞增殖。在 MEHP 处理 24 小时后，出现剂量依赖性的 G2/M 细胞周期停滞以及 DNA 合成急剧下降。在细胞系的 NGF 诱导分化过程中，4 天的 MEHP 暴露（2.5-250 μM）增加了膜和细胞骨架蛋白含量，增强了 NGF 诱导的轴突生长，上调了胆碱乙酰转移酶（ChAT）mRNA 并下调了酪氨酸羟化酶（TH）mRNA 水平，提示以乙酰胆碱（ACh）表型为代价促进向胆碱能（ACh）表型分化。综上所述，我们的结果表明，MEHP 通过抑制细胞增殖和促进神经细胞分化，具有干扰神经发育的潜力。
