Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells
Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells
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DOI：
10.3109/17435390.2011.587903
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发表时间：
2012-08-01
期刊：
影响因子：
5
通讯作者：
Carriere, Marie
中科院分区：
文献类型：
--
作者：
Jugan, Mary-Line;Barillet, Sabrina;Carriere, Marie
二氧化钛纳米粒子（TiO2-NP）的大量生产，引发了人们对其对人类健康影响的担忧。本研究的目的是深入表征 TiO2-NPs 对肺细胞的潜在遗传毒性，并将遗传毒性与理化特征（例如，氧化应激）联系起来。例如，尺寸、比表面积、晶相。 A549 细胞暴露于一组直径范围为 12 至 140 nm（锐钛矿或金红石）的 TiO2-NP。一系列补充技术（彗星和微核测定、γ-H2AX 免疫染色、8-氧鸟嘌呤分析、H-2-DCFDA、谷胱甘肽含量、抗氧化酶活性）使我们能够证明，小而球形的 TiO2-NP（锐钛矿和金红石）可诱导 DNA 单链断裂和氧化损伤，以及一般氧化应激。此外，我们还发现这些 NP 通过使 NER 和 BER 途径失活而损害细胞修复 DNA 的能力。因此，这项研究证实了 TiO2-NP 的潜在遗传毒性，这可能会排除它们的致突变性和致癌性。
Titanium dioxide nanoparticles (TiO2-NPs) are produced in large quantities, raising concerns about their impact for human health. The aim of this study was to deeply characterize TiO2-NPs genotoxic potential to lung cells, and to link genotoxicity to physicochemical characteristics, e. g., size, specific surface area, crystalline phase. A549 cells were exposed to a panel of TiO2-NPs with diameters ranging from 12 to 140 nm, either anatase or rutile. A set of complementary techniques (comet and micronucleus assays, gamma-H2AX immunostaining, 8-oxoGuanine analysis, H-2-DCFDA, glutathione content, antioxidant enzymes activities) allowed us to demonstrate that small and spherical TiO2-NPs, both anatase and rutile, induce single-strand breaks and oxidative lesions to DNA, together with a general oxidative stress. Additionally we show that these NPs impair cell ability to repair DNA, by inactivation of both NER and BER pathways. This study thus confirms the genotoxic potential of TiO2-NPs, which may preclude their mutagenicity and carcinogenicity.