Metal-organic framework [H2NMe2]3 [Tb(PDA)3] induces cytotoxic effects and changes DNA methylation-related gene expression in a human fibroblast cell line

Abstract

The lanthanide metal-organic frameworks (lanthanide MOFs) may be utilized for a variety of environmental and human health applications due to its luminescent properties and high thermal and water stability. However, the cytotoxic and epigenetic effects that these produce in human cells are not known. Therefore, we evaluated the cytotoxic effects, internalization and changes in DNA methylation-associated gene expression induced by exposing human fibroblast cells to a Terbium-based MOF (Tb-MOF). For this purpose, cells were exposed to six concentrations (0.05 to 1.6 mg/mL) of [H2NMe2]3 [Tb(PDA)3] for 48 h. SEM, Confocal microscopy and EDS analysis were performed. Cytotoxicity was determined with the 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 dose-dependent toxicity. Additionally, we detected significant changes in the gene expression levels of DNA methyltransferases and demethylases (important regulators of cell development) due to the presence of Tb-MOF, suggesting that Tb-MOF could generate epigenetic changes even at low concentrations. 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.