Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles.
Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles.
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DOI：
10.2147/ijn.s42028
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发表时间：
2013
影响因子：
8
通讯作者：
Alhadlaq HA
中科院分区：
文献类型：
--
作者：
Alarifi S;Ali D;Alkahtani S;Verma A;Ahamed M;Ahmed M;Alhadlaq HA
氧化锌（ZnO）纳米颗粒在全球范围内的广泛使用使人类暴露于其不良影响，因此了解其生物学效应和任何相关风险非常重要。本研究旨在探讨氧化锌纳米颗粒对人皮肤黑色素瘤（A375）细胞的细胞毒性、氧化应激和凋亡的影响。MTT [3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazoliumbromide]和基于乳酸脱氢酶的细胞活力测定显示暴露于ZnO纳米颗粒后细胞活力显著降低，相差图像显示用这些纳米颗粒处理的细胞具有较低的密度和圆形形态。还发现ZnO纳米颗粒会诱导氧化应激，这一点通过活性氧簇的产生和抗氧化剂谷胱甘肽的消耗得到证明。通过染色体凝集试验和半胱天冬酶-3激活证实了细胞凋亡的诱导。此外，在暴露于最高浓度的ZnO纳米颗粒的细胞中观察到更多的DNA损伤。这些结果表明，ZnO纳米粒子在A375细胞中具有潜在的遗传毒性，这可能是通过氧化应激介导的。我们的短期暴露研究表明，诱导的遗传毒性和细胞凋亡反应的ZnO纳米粒子需要进一步调查，以确定是否有可能长期暴露于ZnO纳米粒子的后果。
The widespread use of zinc oxide (ZnO) nanoparticles worldwide exposes humans to their adverse effects, so it is important to understand their biological effects and any associated risks. This study was designed to investigate the cytotoxicity, oxidative stress, and apoptosis caused by ZnO nanoparticles in human skin melanoma (A375) cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] and lactate dehydrogenase-based cell viability assays showed a significant decrease in cell viability after exposure to ZnO nanoparticles, and phase contrast images revealed that cells treated with these nanoparticles had a lower density and a rounded morphology. ZnO nanoparticles were also found to induce oxidative stress, evidenced by generation of reactive oxygen species and depletion of the antioxidant, glutathione. Induction of apoptosis was confirmed by chromosomal condensation assay and caspase-3 activation. Further, more DNA damage was observed in cells exposed to the highest concentration of ZnO nanoparticles. These results demonstrate that ZnO nanoparticles have genotoxic potential in A375 cells, which may be mediated via oxidative stress. Our short-term exposure study showing induction of a genotoxic and apoptotic response to ZnO nanoparticles needs further investigation to determine whether there may be consequences of long-term exposure to ZnO nanoparticles.