UMR3299 CEA-CNRS, Service Interdisciplinaire des Systèmes Moléculaires et Matériaux, Laboratoire Structure et Dynamique par Résonance Magnétique, CEA Saclay, Gif sur Yvette.
Nanotoxicology. 2012 Aug;6(5):501-13. doi: 10.3109/17435390.2011.587903. Epub 2011 Oct 13.
Titanium dioxide nanoparticles (TiO(2)-NPs) are produced in large quantities, raising concerns about their impact for human health. The aim of this study was to deeply characterize TiO(2)-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 TiO(2)-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, H2-DCFDA, glutathione content, antioxidant enzymes activities) allowed us to demonstrate that small and spherical TiO(2)-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 TiO(2)-NPs, which may preclude their mutagenicity and carcinogenicity.
二氧化钛纳米颗粒 (TiO(2)-NPs) 的产量很大，这引起了人们对其对人类健康影响的关注。本研究的目的是深入研究 TiO(2)-NPs 对肺细胞的遗传毒性潜力，并将遗传毒性与理化特性（如粒径、比表面积、晶相）联系起来。A549 细胞暴露于一系列 TiO(2)-NPs 中，这些 NPs 的粒径范围从 12 到 140nm，分别为锐钛矿或金红石。一组互补的技术（彗星和微核试验、γ-H2AX 免疫染色、8-oxoGuanine 分析、H2-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 TiO(2)-NPs，无论是锐钛矿还是金红石，都会诱导 DNA 的单链断裂和氧化损伤，同时还会引发普遍的氧化应激。此外，我们还表明，这些 NPs 通过使 NER 和 BER 途径失活，损害了细胞修复 DNA 的能力。因此，这项研究证实了 TiO(2)-NPs 的遗传毒性潜力，这可能会排除它们的致突变性和致癌性。
