Quantum dot-induced epigenetic and genotoxic changes in human breast cancer cells

Abstract

The staggering array of nanotechnological products, found in our environment and those applicable in medicine, has stimulated a growing interest in examining their long-term impact on genetic and epigenetic processes. We examined here the epigenomic and genotoxic response to cadmium telluride quantum dots (QDs) in human breast carcinoma cells. QD treatment induced global hypoacetylation implying a global epigenomic response. The ubiquitous responder to genotoxic stress, p53, was activated by QD challenge resulting in translocation of p53, with subsequent upregulation of downstream targets Puma and Noxa. Consequential decrease in cell viability was in part prevented by the p53 inhibitor pifithrin-alpha, suggesting that p53 translocation contributes to QD-induced cytotoxicity. These findings suggest three levels of nanoparticle-induced cellular changes: non-genomic, genomic and epigenetic. Epigenetic changes may have long-term effects on gene expression programming long after the initial signal has been removed, and if these changes remain undetected, it could lead to long-term untoward effects in biological systems. These studies suggest that aside from genotoxic effects, nanoparticles could cause more subtle epigenetic changes which merit thorough examination of environmental nanoparticles and novel candidate nanomaterials for medical applications.

Quantum Dot Cytotoxicity and Ways To Reduce It

“…Chromatin reorganization was detected upon exposure of MCF-7 cells to low amounts (5 μg/mL) of green CdTe QDs for 24 h. It was accompanied by a significant change in global hypoacetylation, implying an epigenomic response. 34 The magnitude of the reduction in histone acetylation was inversely proportional to [QD], such that the higher the [QD], the more histone acetylation decreased. These epigenetic changes corresponded with (i) the reduction in the transcription of genes associated with cell death prevention, such as cIAP-1 (inhibitor of apoptosis) and Hsp70 (heat shock protein 70), and the suppression of GPx (glutathione peroxidase) mRNA expression and (ii) the activation of the ubiquitous responder to genotoxic stress, p53, resulting in translocation of p53 with subsequent upregulation of the downstream targets Puma and Noxa ( Figure 5).…”

Synergetic effect of functional cadmium–tellurium quantum dots conjugated with gambogic acid for HepG2 cell-labeling and proliferation inhibition

“…22,23 CdTe QDs can also enter the cell nucleus through nuclear pore complexes in live human macrophages and lead to human breast epithelial cancer cell (MCF-7) death. 24 Thus, CdTe QDs have potential applications as stable fluorescence probes in the field of biomedicine, as well as utility for disease tracing and diagnosis; 25 with functional modifications, CdTe QDs may be widely studied for use in other fields, for instance, for drug delivery or as assistant reagents.…”

Quantum Dots in Biomedical Research

“…Unrestricted interactions of any kind of materials, including QDs, have the potential to be toxic, especially at higher concentration and/or with enhanced adsorption/internalization. Beyond the changes over cell function, more evident effects are prone to be caused by QDs, including cellular ones such: (i) changes in cell morphology (Chang et al, 2009), (ii) oxidative stress (Lovrić, et al, 2005), (iii) release of heavy metal compounds (Kirchner et al, 2005) and (iv) genetic and epigenetic damage (Choi et al, 2008), as well as local inflammation in live rats, as we have recently reported.…”