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首页> 外文期刊>Toxicological sciences: An official journal of the Society of Toxicology >Study of TiO2 P25 Nanoparticles Genotoxicity on Lung, Blood, and Liver Cells in Lung Overload andNon-Overload ConditionsAfter Repeated Respiratory Exposure in Rats
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Study of TiO2 P25 Nanoparticles Genotoxicity on Lung, Blood, and Liver Cells in Lung Overload andNon-Overload ConditionsAfter Repeated Respiratory Exposure in Rats

机译：肺，血液和肝细胞在肺，血液和肝细胞中的TiO2 P25纳米粒子遗传毒性研究大鼠重复呼吸暴露的反复呼吸道暴露

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Inhaled titanium dioxide (TiO2) nanoparticles (NPs) can have negative health effects, and have been shown to cause respiratory tract cancer in rats. Inflammation has been linked to oxidative stress, and both have been described as possible mechanisms for genotoxicity of NPs, but rarely examined side-by-side in animal studies. In the present study, a wide range of complementary endpoints have been performed to study TiO2 P25NP-induced genotoxicity in lung overload and non-overload conditions. Additionally, lung burden, inflammation, cytotoxicity and oxidative stress have also been evaluated in order to link genotoxicity with these responses. To assess quick and delayed responses after recovery, endpoints were evaluated at two time points: 2 h and 35 days after three repeated instillations. This study confirmed the previously described lung overload threshold at approximately 200-300cm(2) of lung burden for total particle surface area lung deposition or 4.2 ml/kg for volume-based cumulative lung exposure dose, above which lung clearance is impaired and inflammation is induced. Our results went on to show that these overload doses induced delayed genotoxicity in lung, associated with persistent inflammation only at the highest dose. The lowest tested doses had no toxicity or genotoxicity effects in the lung. In blood, no lymphocyte DNA damage, erythrocytes chromosomal damage or gene mutation could be detected. Our data also demonstrated that only overload doses induced liver DNA lesions irrespective of the recovery time. Tested doses of TiO2 P25 NPs did not induce glutathione changes in lung, blood or liver at both recovery times.
机译：吸入二氧化钛（TiO 2）纳米颗粒（NPS）可具有负性健康效果，并且已被证明在大鼠中引起呼吸道癌症。炎症与氧化应激有关，两者都被描述为NPS的遗传毒性的可能机制，但在动物研究中很少被另一侧检查。在本研究中，已经进行了广泛的互补终点，以研究肺重载和非过载条件中的TiO2 P25NP诱导的遗传毒性。另外，还评估了肺负荷，炎症，细胞毒性和氧化应激，以便将遗传毒性与这些反应联系起来。为了评估恢复后的快速和延迟响应，终点被评估为两个时间点：三次重复滴注后2小时和35天。该研究证实了前面描述的肺重载阈值大约200-300cm（2）的肺负荷，用于总颗粒表面积肺沉积或基于体积的体积累积肺暴露剂量的4.2ml / kg，以上肺部间隙受损，炎症是肿瘤诱导。我们的结果继续表明，这些过载剂量在肺中诱导延迟遗传毒性，仅在最高剂量下与持续炎症相关联。最低测试剂量在肺中没有毒性或遗传毒性作用。在血液中，不能检测到淋巴细胞DNA损伤，红细胞染色体损伤或基因突变。我们的数据还表明，无论恢复时间如何，只有过载剂量诱导肝脏DNA病变。测试剂量的TiO2 P25 NPS在恢复时间内没有诱导肺癌，血液或肝脏的谷胱甘肽变化。

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