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体外氧化锆纳米颗粒的影响:V-79 细胞的摄取、遗传毒性和致突变性。

In Vitro Effects of Zirconia Nanoparticles: Uptake, Genotoxicity, and Mutagenicity in V-79 cells.

机构信息

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India.

Nanomaterial Toxicology Laboratory, Drug and Chemical Toxicology Group (FEST), CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, P.O. Box 80, Lucknow-226001, India.

出版信息

Biol Trace Elem Res. 2024 Mar;202(3):927-940. doi: 10.1007/s12011-023-03739-4. Epub 2023 Jul 13.

Abstract

Zirconia nanoparticles are used in various industrial and biomedical applications such as dental implants, thermal barrier sprays, and fuel cells. The interaction of nanoparticles with the environment and humans is inevitable. Despite the enormous application potential of these nanoparticles, there are still some gaps in the literature regarding potential toxicological mechanisms and the genotoxicity of zirconia nanoparticles. The lung is one of the main exposure routes to nanomaterials; therefore, the present study was designed to determine the genotoxic and mutagenic effect of zirconia NPs in V-79 lung cells. Zirconia nanoparticles showed significant internalization in cells at 100 μg/mL and 150 μg/mL concentrations. Zirconia nanoparticles showed low cytotoxicity and were found to generate ROS in V-79 cells. In alkaline comet assay, zirconia nanoparticles (10 μg/mL, 50 μg/mL, and 100 μg/mL) exposed cells exhibited significant DNA strand breaks, while the neutral comet assay, which was used for double-strand break assessment, only revealed significant damage at 100 μg/mL. Chromosomal aberration induced by zirconia nanoparticles mainly resulted in the generation of gaps, few fragments, and breaks which signifies the low clastogenic activity of these nanoparticles in the V-79 cell line. In MN assay, zirconia nanoparticles resulted in no significant micronuclei induction at any given concentration. In the HPRT mutation assay, the particle shows a dose-dependent increase in the mutant frequency. It is evident from the result that zirconia nanoparticles cause dose-dependent cytotoxicity and genotoxicity, but still, more studies are needed to evaluate the clastogenic potential and the possible mechanism involved.

摘要

氧化锆纳米颗粒在各种工业和生物医学应用中得到广泛应用,如牙科植入物、热障喷雾和燃料电池。纳米颗粒与环境和人类的相互作用是不可避免的。尽管这些纳米颗粒具有巨大的应用潜力,但关于其潜在毒理学机制和氧化锆纳米颗粒的遗传毒性,文献中仍存在一些空白。肺部是纳米材料主要暴露途径之一;因此,本研究旨在确定氧化锆 NPs 在 V-79 肺细胞中的遗传毒性和致突变性。氧化锆纳米颗粒在 100μg/mL 和 150μg/mL 浓度下在细胞内显示出明显的内化。氧化锆纳米颗粒表现出低细胞毒性,并在 V-79 细胞中产生 ROS。在碱性彗星试验中,氧化锆纳米颗粒(10μg/mL、50μg/mL 和 100μg/mL)暴露的细胞显示出明显的 DNA 链断裂,而用于双链断裂评估的中性彗星试验仅在 100μg/mL 时显示出明显的损伤。氧化锆纳米颗粒诱导的染色体畸变主要导致间隙的产生,片段和断裂较少,这表明这些纳米颗粒在 V-79 细胞系中的遗传毒性活性较低。在 MN 试验中,氧化锆纳米颗粒在任何给定浓度下均未导致明显的微核诱导。在 HPRT 突变试验中,颗粒显示出剂量依赖性的突变频率增加。结果表明,氧化锆纳米颗粒引起剂量依赖性的细胞毒性和遗传毒性,但仍需要更多的研究来评估其断裂剂潜力和可能涉及的机制。

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