不同表面修饰的氧化铁纳米颗粒对A549细胞的毒性及DNA损伤

doi:10.3969/j.issn.1004-616x.2018.06.001

Abstract

Abstract: OBJECTIVE: To compare the induction of cytotoxicity,chromosome aberrations and DNA damage among iron oxide nanoparticles (IONPs) with different surface-modifications in A549 cells. METHODS: The effects of amine-modified (Amine-IONP) and polyethylene glycol-modified iron oxide nanoparticles (PEG-IONP) of the same particle size range (5 nm) on cell viability and cell cycle were compared in A549 cells;the content of intracellular reactive oxygen species (ROS),mitochondrial membrane potential (MMP) and endoplasmi reticulum stress (ERS) in cells treated with IONPs were analyzed using high content screening method;the in vitro cytokinesis micronucleus test and Comet assay were performed to evaluate their effects on chromosome and DNA integrity. RESULTS: The growth inhibitory rates of both IONPs to A549 cells were less than 20% after 48 h. Under the same concentration,PEG-IONP exhibited a more significant effect on the G0/G1 cell cycle arrest (P < 0.05):the initial concentration to significantly reduce the cell rate of S phase was 20 μg/mL,and the expression of p21 and p53 was up-regulated by a treatment of 320 μg/mL PEG-IONP for 24 h (P < 0.05). After a 48 h treatment,the initial concentrations to show significant effects of Amine-IONP on ROS,MMP and ER were 20,20 and 80 μg/mL,while for PEG-IONP they were 40, 40 and 160 μg/mL respectively. In addition,compared to PEG-IONP,Amine-IONP was able to induce the formation of micronuclei and Comet tail (the initial concentrations for Amine-IONP were 20 and 80 μg/mL;while PEG-IONP were 40 and 160 μg/mL respectively). After the pre-treatment with oxygen free radical scavengers N-acetylcysteine and butylated hydroxyanisole,both IONPs induced ROS and Comet DNA Tail were significantly inhibited (P < 0.05). CONCLUSION: Positively charged Amine-IONP was more effective in inducing oxidative stress and DNA damage in A549 cells;whereas,PEG-IONP with relatively weaker cytotoxicity and genotoxicity interfered with cell proliferation,and showed advantages in the development of tumor diagnostic reagents.

Key words: iron oxide nanoparticles, A549 cells, micronucleus assay, Comet assay, oxidative stress, cell proliferation

CLC Number:

R917

WEN Hairuo, GUO Yajuan, HUANG Zhiying, WANG Xue, DAN Mo. Induction of cytotoxicity and DNA damage by iron oxide nanoparticles with different surface modifications in A549 cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(6): 413-421.

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Induction of cytotoxicity and DNA damage by iron oxide nanoparticles with different surface modifications in A549 cells

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