Toxicity of nano- and micro-sized ZnO particles in human lung epithelial cells
Toxicity of nano- and micro-sized ZnO particles in human lung epithelial cells
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DOI：
10.1007/s11051-008-9419-7
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发表时间：
2009-01-01
影响因子：
2.5
通讯作者：
Huang, Yue-Wern
中科院分区：
文献类型：
--
作者：
Lin, Weisheng;Xu, Yi;Huang, Yue-Wern
这是第一个评估70 nm和420 nm氧化锌颗粒对人肺癌细胞(A549)细胞毒性、毒性生化机制和DNA氧化损伤的综合研究。在相当小的剂量范围内，两种大小的颗粒都会以剂量和时间依赖的方式显著降低细胞存活率。基于颗粒质量的剂量测定和基于颗粒比表面积的剂量测定在70 nm和420 nm的氧化锌颗粒中都产生了两种不同的细胞毒性模式。活性氧(ROS)水平升高导致细胞内氧化应激、脂质过氧化、细胞膜渗漏和DNA氧化损伤。N-乙酰半胱氨酸对氧化锌诱导的细胞毒性的保护作用进一步表明氧化应激参与了细胞毒性。游离锌离子的细胞毒性、细胞培养液中锌离子的解离程度和电感耦合等离子体质谱金属分析表明，游离锌离子和金属杂质不是ROS诱导的主要因素。我们得出的结论是：(1)暴露在两种尺寸的氧化锌颗粒中都会导致剂量和时间依赖性的细胞毒性，表现为氧化应激、脂质过氧化、细胞膜损伤和DNA氧化损伤；(2)氧化锌颗粒表现出其他金属氧化物中没有的更陡峭的剂量-反应模式；(3)氧化锌颗粒样品中的游离锌离子和金属杂质都不是细胞毒性的原因。
This is the first comprehensive study to evaluate the cytotoxicity, biochemical mechanisms of toxicity, and oxidative DNA damage caused by exposing human bronchoalveolar carcinoma-derived cells (A549) to 70 and 420 nm ZnO particles. Particles of either size significantly reduced cell viability in a dose- and time-dependent manner within a rather narrow dosage range. Particle mass-based dosimetry and particle-specific surface area-based dosimetry yielded two distinct patterns of cytotoxicity in both 70 and 420 nm ZnO particles. Elevated levels of reactive oxygen species (ROS) resulted in intracellular oxidative stress, lipid peroxidation, cell membrane leakage, and oxidative DNA damage. The protective effect of N-acetylcysteine on ZnO-induced cytotoxicity further implicated oxidative stress in the cytotoxicity. Free Zn2+ and metal impurities were not major contributors of ROS induction as indicated by limited free Zn2+ cytotoxicity, extent of Zn2+ dissociation in the cell culture medium, and inductively-coupled plasma-mass spectrometry metal analysis. We conclude that (1) exposure to both sizes of ZnO particles leads to dose- and time-dependent cytotoxicity reflected in oxidative stress, lipid peroxidation, cell membrane damage, and oxidative DNA damage, (2) ZnO particles exhibit a much steeper dose-response pattern unseen in other metal oxides, and (3) neither free Zn2+ nor metal impurity in the ZnO particle samples is the cause of cytotoxicity.