Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.
Department of translational and precision medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Int J Mol Sci. 2020 Feb 25;21(5):1556. doi: 10.3390/ijms21051556.
Exposure to environmental endocrine disruptors has been associated with an increased frequency of thyroid pathology. In this study, we evaluated the effects of various concentrations of methylmercury (MeHg) on immortalized, non-tumorigenic thyroid cells (Nthy-ori-3-1). Exposure to MeHg at 2.5 and 5 µM for 24 h caused a reduction in cell viability with a decrease of the cell population in sub-G0 phase, as detected by MTT and flow cytometry. Conversely, MeHg at the lower concentration of 0.1 µM increased the cell viability with a rise of G2/M phase. An immunoblot analysis showed higher expression levels of phospho-ERK and not of phospho-Akt. Further enhancement of the cell growth rate was observed after a prolonged exposure of the cells up to 18 days to MeHg 0.1 µM. The present findings demonstrate the toxicity of high concentrations of MeHg on thyroid cells, while showing that treatment with lower doses of Hg, as may occur after prolonged exposure to this environmental contaminant, exerts a promoting effect on thyroid cell proliferation, by acting on the ERK-mediated pro-oncogenic signal transduction pathway.
环境内分泌干扰物的暴露与甲状腺病理学的发生频率增加有关。在这项研究中，我们评估了不同浓度的甲基汞（MeHg）对永生化、非致瘤性甲状腺细胞（Nthy-ori-3-1）的影响。暴露于 2.5 和 5 μM 的 MeHg 24 小时可导致细胞活力降低，通过 MTT 和流式细胞术检测到亚 G0 期细胞群体减少。相反，较低浓度的 0.1 μM MeHg 可增加细胞活力，导致 G2/M 期升高。免疫印迹分析显示磷酸化 ERK 的表达水平升高，而磷酸化 Akt 的表达水平没有升高。在将细胞暴露于 0.1 μM MeHg 长达 18 天后，观察到细胞生长速度进一步增强。本研究结果表明高浓度 MeHg 对甲状腺细胞具有毒性，而表明在长时间暴露于这种环境污染物后，用较低剂量的 Hg 处理可通过作用于 ERK 介导的致癌信号转导通路对甲状腺细胞增殖产生促进作用。
