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二氧化钛纳米颗粒对人外周血单个核细胞DNA甲基化的影响。

Effect of titanium dioxide nanoparticles on DNA methylation of human peripheral blood mononuclear cells.

作者信息

Malakootian Mohammad, Nasiri Alireza, Osornio-Vargas Alvaro R, Faraji Maryam

机构信息

Environmental Health Engineering Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Department of Pediatrics, University of Alberta, 3-591 Edmonton Clinic Health Academy, Edmonton T6G 1C9, Canada.

出版信息

Toxicol Res (Camb). 2021 Aug 31;10(5):1045-1051. doi: 10.1093/toxres/tfab085. eCollection 2021 Oct.

Abstract

The aim of the current study was to investigate the effect of well-characterized TiO nanoparticles on DNA methylation of peripheral blood mononuclear cells (PBMCs) . Maximum non-toxic concentration of nanoparticles for PBMCs was determined by MTT assay. The effect of TiO nanoparticles at concentrations of 25-100 μg/ml on DNA methylation of PBMCs was investigated by measuring the %5-mC alterations through an ELISA assay. The physicochemical analysis showed that the TiO nanoparticles were crystalline, pure and in the anatase phase. Peaks related to Ti-O tensile vibrations were observed in the range of 1510 cm. The size of nanoparticles was in the range of 39-74 nm with an average hydrodynamic diameter of 43.82 nm. According to the results of the MTT test, 100 μg/ml was found to be maximum non-toxic concentration. The %5-mC in treated PBMCs revealed that TiO nanoparticles could lead to DNA hypomethylation in PBMCs. The %5-mC difference compared with the negative control was found to be 2.07 ± 1.02% ( = 0.03). The difference of %5-mC between the 25 and 100 μg/ml concentration of nanoparticles was statistically significant ( = 0.02). The results of the current study show that the TiO nanoparticles cause DNA hypomethylation in PBMCs in a dose-response manner. Therefore, it is recommended to evaluate the effects of cytotoxicity and epigenotoxicity of commonly used nanoparticles before their use.

摘要

本研究的目的是调查特性明确的二氧化钛纳米颗粒对外周血单核细胞(PBMCs)DNA甲基化的影响。通过MTT试验确定纳米颗粒对PBMCs的最大无毒浓度。通过ELISA试验测量5-甲基胞嘧啶(5-mC)变化百分比,研究浓度为25-100μg/ml的二氧化钛纳米颗粒对PBMCs DNA甲基化的影响。物理化学分析表明,二氧化钛纳米颗粒为结晶态、纯净且处于锐钛矿相。在1510cm范围内观察到与Ti-O拉伸振动相关的峰。纳米颗粒尺寸在39-74nm范围内,平均流体动力学直径为43.82nm。根据MTT试验结果,发现100μg/ml为最大无毒浓度。处理后的PBMCs中的5-mC百分比表明,二氧化钛纳米颗粒可导致PBMCs中的DNA低甲基化。与阴性对照相比,5-mC差异为2.07±1.02%(P=0.03)。纳米颗粒浓度在25μg/ml和100μg/ml之间时,5-mC差异具有统计学意义(P=0.02)。本研究结果表明,二氧化钛纳米颗粒以剂量反应方式导致PBMCs中的DNA低甲基化。因此,建议在使用常用纳米颗粒之前评估其细胞毒性和表观遗传毒性作用。

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