Inorganic mercury pre-exposures protect against methyl mercury toxicity in NSC-34 (neuron x spinal cord hybrid) cells

Inorganic mercury pre-exposures protect against methyl mercury toxicity in NSC-34 (neuron x spinal cord hybrid) cells
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DOI:
10.1016/s0300-483x(98)00151-6
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发表时间:
1999-02-15
期刊:
影响因子:
4.5
通讯作者:
Chan, HM
Chan, HM
中科院分区:
医学3区
文献类型:
--
作者:
Chapman, LA;Chan, HM

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本文报道了一种来源于新生小鼠的神经元脊髓X杂交细胞(NSC-34),用于汞毒性研究。NSC-34细胞暴露于氯化甲基汞(MeHgCl)(0-16 μ M)导致显著的剂量依赖性细胞损伤和死亡(P < 0.05)。MeHgCl对NSC-34细胞及其亲本细胞株N18 TG-2的毒性均高于无机汞(Hg 2+)(P < 0.05)。Hg ~(2+)可诱导MT的表达(P < 0.05),而Zn ~(2+)和甲基汞则无此作用。为了模拟长期暴露于MeHg的哺乳动物脑中Hg 2+的增加,在暴露于MeHgCl(1-16 μ M)48小时之前,将细胞用1 μ M氯化汞(HgCl 2)处理5代。通过台盼蓝拒染、刃天青染料还原和酸性磷酸酶活性测定MeHgCl毒性。台盼蓝拒染法(P = 0.0559)和刃天青还原法(P = 0.0001)显示,预先暴露于HgCl 2可减轻毒性。HgCl 2预暴露也可诱导MT的产生(P = 0.0066),并减轻还原型谷胱甘肽(GSH)的下降(P = 0.0013)。提示MT和GSH对甲基汞引起的脊髓神经元细胞毒性具有保护作用。NSC-34杂交鳗可作为甲基汞神经毒性研究的一个有用模型。(C)1999爱思唯尔科学爱尔兰有限公司保留所有权利。
A neuron spinal chord x hybrid (NSC-34) cell culture derived from neonatal mouse was characterized for studies on mercury toxicity. Exposure of NSC-34 cells to methyl mercury chloride (MeHgCl) (0-16 mu M) resulted in significant dose-dependent cell damage and death (P < 0.05). MeHgCl was more toxic than inorganic mercury (Hg2+) for both the NSC-34 cells and its parent neuroblastoma cell line N18TG-2 (P < 0.05). Hg2+, but not ZnCl2 or MeHg exposure induced metallothionein (MT) (P < 0.05). To mimic the increase in Hg2+ in the mammalian brain with long term MeHg exposure, the cells were treated with 1 mu M mercuric chloride (HgCl2) for five passages before exposure to MeHgCl (1-16 mu M) for 48 h. MeHgCl toxicity was measured by trypan blue exclusion, reduction of resazurin dye and acid phosphatase activity. Pre-exposure to HgCl2 lessened the toxicity as shown by trypan blue exclusion (P = 0.0559) and reduction of resazurin (P = 0.0001). Pre-exposure to HgCl2 also resulted in induction of MT (P = 0.0066) and lessened the decrease of reduced glutathione (GSH) (P = 0.0013). These results suggest that MT and GSH may play a protective role in methyl mercury induced neurotoxicity of neuron spinal chord cells. The NSC-34 hybrid eel line can be a useful model for the study of MeHg neurotoxicity. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.