Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice.
Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice.
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DOI：
10.1158/0008-5472.can-09-2496
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发表时间：
2009-11-15
期刊：
影响因子：
11.2
通讯作者：
Schiestl RH
中科院分区：
文献类型：
--
作者：
Trouiller B;Reliene R;Westbrook A;Solaimani P;Schiestl RH
二氧化钛（TiO 2）纳米颗粒（NPs）在世界范围内大量生产，用于广泛的应用，包括颜料和化妆品制造。虽然TiO 2是化学惰性的，但TiO 2纳米颗粒可能会对健康产生负面影响，如大鼠呼吸道癌症。然而，TiO 2诱导的遗传毒性和致癌性的机制尚未明确定义，并且在体内研究不足。本研究在小鼠模型中研究了TiO 2 NP诱导的遗传毒性、氧化性DNA损伤和炎症。我们在饮用水中加入TiO 2纳米颗粒处理野生型小鼠，并使用彗星试验、微核试验、γ-H2 AX免疫染色试验和通过测量8-羟基-2 ′-脱氧鸟苷（8-OHdG）水平以及作为遗传不稳定性终点的DNA缺失来确定DNA损伤的程度。我们还测定了外周血中炎性细胞因子的mRNA水平。我们的研究结果表明，TiO 2纳米颗粒诱导8-OHdG，γ-H2 AX焦点，微核和DNA缺失。表明DNA双链断裂的γ-H2 AX灶的形成是最敏感的参数。还存在炎症，其特征在于中度炎症反应。这些结果共同描述了TiO 2 NP诱导的小鼠体内遗传毒性的首次全面研究，可能由与炎症和/或氧化应激相关的继发性遗传毒性机制引起。鉴于TiO 2 NP的使用越来越多，这些发现引起了对与TiO 2 NP暴露相关的潜在健康危害的关注。
Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications including pigment and cosmetic manufacturing. Although TiO2 is chemically inert, TiO2 NPs can cause negative health effects, like respiratory tract cancer in rats. However, the mechanisms involved in TiO2-induced genotoxicity and carcinogenicity have not been clearly defined and are poorly studied in vivo. The present study investigates TiO2 NP-induced genotoxicity, oxidative DNA damage and inflammation in a mice model. We treated wild type mice with TiO2 NPs in drinking water and determined the extent of DNA damage using the comet assay, the micronuclei assay, the γ-H2AX immuno-staining assay and by measuring 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels and, as genetic instability end point, DNA deletions. We also determined mRNA levels of inflammatory cytokines in the peripheral blood. Our results show that TiO2 NPs induced 8-OHdG, γ-H2AX foci, micronuclei and DNA deletions. The formation of γ-H2AX foci, indicative of DNA double strand breaks, was the most sensitive parameter. Inflammation was also present as characterized by a moderate inflammatory response. Together these results describe the first comprehensive study of TiO2 NP induced genotoxicity in vivo in mice, possibly caused by a secondary genotoxic mechanism associated with inflammation and/or oxidative stress. Given the growing use of TiO2 NPs, these findings raise concern about potential health hazards associated with TiO2 NP exposure.