Comparison of Cytotoxicity and Inhibition of Membrane ABC Transporters Induced by MWCNTs with Different Length and Functional Groups
Comparison of Cytotoxicity and Inhibition of Membrane ABC Transporters Induced by MWCNTs with Different Length and Functional Groups
复制标题
不同长度和官能团的多壁碳纳米管对膜ABC转运蛋白的细胞毒性和抑制作用比较
DOI：
10.1021/acs.est.5b05772
复制
发表时间：
2016
影响因子：
11.4
通讯作者：
Li Mei
中科院分区：
文献类型：
--
作者：
Yu Jing;Liu Su;Wu Bing;Shen Zhuoyan;Cherr Gary N.;Zhang Xu-xiang;Li Mei
实验研究表明，多壁碳纳米管（MWCNTs）具有诱导细胞毒性的潜力。然而，报告往往前后不一，甚至相互矛盾。此外，MWCNT在低浓度下的不利影响还没有得到很好的理解。本研究系统比较了两种不同长度（0.5-2 μm和10-30 μm）的6种多壁碳纳米管（包括原始多壁碳纳米管、羟基多壁碳纳米管和羧基多壁碳纳米管）对人肝癌细胞株HepG 2的毒性作用。结果表明，多壁碳纳米管通过增加活性氧（ROS）的产生和破坏细胞功能诱导细胞毒性。原始的短MWCNT比原始的长MWCNT诱导更高的细胞毒性。功能化增加了长多壁碳纳米管的细胞毒性，但减少了短多壁碳纳米管的细胞毒性。此外，我们的研究结果表明，在无毒浓度下，六种多壁碳纳米管可能不对环境安全，因为它们抑制ABC转运蛋白的外排能力。即使在非常低的浓度下也观察到这种抑制作用，该浓度比其对细胞毒性的有效浓度低40-1000倍。ABC转运蛋白的抑制显着增加砷的细胞毒性，ABC转运蛋白的已知底物，表明多壁碳纳米管的化学增敏作用。质膜损伤可能是六种多壁碳纳米管抑制ABC转运蛋白活性的机制。这项研究提供了深入了解环境中低水平的多壁碳纳米管的风险评估。
Experimental studies indicate that multiwalled carbon nanotubes (MWCNTs) have the potential to induce cytotoxicity. However, the reports are often inconsistent and even contradictory. Additionally, adverse effects of MWCNTs at low concentration are not well understood. In this study, we systemically compared adverse effects of six MWCNTs including pristine MWCNTs, hydroxyl-MWCNTs and carboxyl-MWCNTs of two different lengths (0.5–2 μm and 10–30 μm) on human hepatoma cell line HepG2. Results showed that MWCNTs induced cytotoxicity by increasing reactive oxygen species (ROS) generation and damaging cell function. Pristine short MWCNTs induced higher cytotoxicity than pristine long MWCNTs. Functionalization increased cytotoxicity of long MWCNTs, but reduced cytotoxicity of short MWCNTs. Further, our results indicated that the six MWCNTs, at nontoxic concentration, might not be environmentally safe as they inhibited ABC transporters’ efflux capabilities. This inhibition was observed even at very low concentrations, which were 40–1000 times lower than their effective concentrations on cytotoxicity. The inhibition of ABC transporters significantly increased cytotoxicity of arsenic, a known substrate of ABC transporters, indicating a chemosensitizing effect of MWCNTs. Plasma membrane damage was likely the mechanism by which the six MWCNTs inhibited ABC transporter activity. This study provides insight into risk assessments of low levels of MWCNTs in the environment.