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金属有机框架化合物[HNMe][Tb(III)(2,6-吡啶二甲酸酯)](Tb-MOF)对人成纤维细胞系的细胞毒性作用诱导及DNA甲基化相关基因表达的变化

Induction of cytotoxic effects and changes in DNA methylation-related gene expression in a human fibroblast cell line by the metal-organic framework [HNMe] [Tb(III)(2,6 pyridinedicarboxylate)] (Tb-MOF).

作者信息

Carrillo-Cocom Leydi Maribel, Juárez-Méndez Lucia, Rincón Susana, Rivera-Villanueva José María, Nic-Can Geovanny Iran, Zepeda Alejandro

机构信息

Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Campus de Ingenierías y Ciencias Exactas, periférico norte km 33.5, C.P. 97203, Mérida, Yucatán, México.

Tecnológico Nacional de México/I.T. Mérida, Av. Tecnológico S/N, C.P. 97118, Mérida, Yucatán, México.

出版信息

Environ Sci Pollut Res Int. 2023 Apr;30(16):46685-46696. doi: 10.1007/s11356-023-25314-z. Epub 2023 Feb 1.

Abstract

Lanthanide metal-organic frameworks (lanthanide MOFs) may be utilized for a variety of environmental and human health applications due to their luminescent properties and high thermal and water stability. However, the cytotoxic and epigenetic effects produced in human cells are not known. Therefore, we evaluated the cytotoxic effects, internalization, and changes in the mRNA abundance of DNA methylation and demethylation enzymes by exposing human fibroblast cells to a metal-organic framework [HNMe] [Tb(III)(2,6 pyridinedicarboxylate)] (Tb-MOF). For this purpose, the cells were exposed to six concentrations (0.05 to 1.6 mg/mL) of Tb-MOF for 48 h. Field emission electron microscopy coupled to linear energy dispersive spectroscopy (FESEM‒EDS) and confocal microscopy analysis were performed. The cytotoxicity was determined with crystal violet and MTT assays. The results demonstrated the internalization of Tb-MOF at concentrations as low as 0.05 mg/mL, as well as concentration-dependent toxicity. Additionally, we detected significant changes in the gene expression levels of DNA methyltransferases and demethylases due to the presence of Tb-MOF, suggesting that Tb-MOF could generate epigenetic changes even at low concentrations. The results of our study may establish a foundation for future research attempting to develop and apply secure nanomaterials (e.g., MOFs) to minimize damage to the environment and human health.

摘要

镧系金属有机框架材料(镧系MOF)由于其发光特性以及高热稳定性和水稳定性,可用于多种环境和人类健康应用。然而,其在人类细胞中产生的细胞毒性和表观遗传效应尚不清楚。因此,我们通过将人类成纤维细胞暴露于金属有机框架材料[HNMe][Tb(III)(2,6-吡啶二甲酸酯)](Tb-MOF),评估了细胞毒性效应、内化情况以及DNA甲基化和去甲基化酶的mRNA丰度变化。为此,将细胞暴露于六种浓度(0.05至1.6 mg/mL)的Tb-MOF中48小时。进行了场发射电子显微镜与线性能量色散光谱联用(FESEM-EDS)以及共聚焦显微镜分析。通过结晶紫和MTT法测定细胞毒性。结果表明,Tb-MOF在低至0.05 mg/mL的浓度下即可内化,且具有浓度依赖性毒性。此外,我们检测到由于Tb-MOF的存在,DNA甲基转移酶和去甲基酶的基因表达水平发生了显著变化,这表明Tb-MOF即使在低浓度下也可能产生表观遗传变化。我们的研究结果可能为未来旨在开发和应用安全纳米材料(如MOF)以尽量减少对环境和人类健康损害的研究奠定基础。

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