Cytotoxic and Genotoxic Effects of Cadmium Sulfide Nanoparticles

Abstract

Cadmium compounds are highly toxic substances characterized by mutagenic, genotoxic and carcinogenic effects, and having high cumulative properties. Application of cadmium nanoparticles (NPs) in medicine stimulates the study of their mechanism of action at the cellular level and at the level of organs and systems, determination of biomarkers of their action, particularly in comparison with the ionic form. The aim of the study was to compare the features of cytotoxic and genotoxic effects of cadmium sulfide (CdS) NPs of different sizes on cell cultures of different histogenesis with those of cadmium chloride (CdCl2). Materials and Methods: In this work, we used cadmium compounds in the nanoform: NPs CdS of 4–6 nm and of 9–11 nm in size; and in the ionic form: CdCl2. The studies were conducted in vitro in cell lines — IMR-32, НEК-293 and MАEC. To count viable cells we compared the results of three basic tests: MTT (methyl tetrasolium test), SRB (sulforhodamine B test) and NRU (neutral red uptake test). We evaluated the genotoxic effect of the substances studied in vitro using DNA comet assay in alkaline conditions. Results: CdS NPs and CdCl2 demonstrated pronounced dose-dependent cytotoxic effect in MАEC, НEК-293 and IMR-32 cell lines, by impairing membrane permeability, functioning of mitochondria and lysosomes, and inhibiting the function of protein synthesis. Cytotoxic effect of CdCl2 was the most pronounced, this effect of CdS NPs of 9–11 nm in size being the least pronounced. The comet DNA assay in alkaline conditions revealed a statistically significant increase in DNA comet index when exposed to CdCl2 and CdS NPs in comparison with the negative control, which indicates their genotoxic effect. CdS NPs of 4–6 nm in size showed a more pronounced effect in comparison with those of 9–11 nm in size. Conclusion: Elucidation of mechanisms underlying the implementation of toxic effects of cadmium NPs will help in assessing the potential risks associated with their use in industry and developing effective preventive measures. For instance, when planning in vivo studies for toxicological evaluation of nanomaterials and nano-substances containing NPs of cadmium, it is necessary to investigate the mutagenic and carcinogenic risks and to take into account the high likelihood of neurotoxic and cardiovasotoxic effects, along with nephrotoxic effects, since high cytotoxic activity of the investigated compounds of cadmium was detected on the cells of the MАEC line (endothelial origin) and IMR-32 (neuronal origin).

Suitability of a Cellulose-Based Nanomaterial for the Remediation of Heavy Metal Contaminated Freshwaters: A Case-Study Showing the Recovery of Cadmium Induced DNA Integrity Loss, Cell Proliferation Increase, Nuclear Morphology and Chromosomal Alterations on Dreissena polymorpha

“…It was proposed that it is multi-factorial [49], and an important role may be played by the indirect increase of reactive oxygen species and the disruption of the cellular antioxidant system [12,50,51], leading to oxidative stress induction [52], which, in turn, causes lesions to the DNA, including potentially lethal DSBs [13]. It also competes with Zn (II) in cellular components and binds to the DNA bases, giving rise to single-stranded DNA breaks [53,54]. While the European Union directive posed 0.005 mg L −1 of cadmium as a threshold for drinking water, other countries allowed higher thresholds to be set for freshwater.…”

“…Interestingly, after 2 day-exposure the frequency of binucleated hemocytes turned down to control level in specimens exposed to cadmium in AFW treated with CNS (Cd-t CNS) ( Figure 4). Cadmium was actually found to stimulate DNA synthesis and cell proliferation at low concentrations in mammalian cell lines [54], leading to relevant implications for carcinogenesis processes. An increased level of binucleated gill cells has been also observed in zebra mussel after 5 days of exposure and proposed to be related to an inhibition of cytokinesis activity more than a Cd proliferative effect [1].…”

“…Cd-induced biochemical changes may play roles in all the stages of carcinogenicity and the induction of oxidative stress in combination with decreased DNA repair can lead to DNA damage [54]. It has been proposed that Cd interferes with major DNA repair systems [13], leading to their inhibition [67,68], and unrepaired DNA lesions may give rise to chromosomal damage.…”

Cadmium exposure enhances VE‑cadherin expression in endothelial cells via suppression of ROCK signaling

“…Cadmium (Cd) is one of the global pollutants of the environment (1). Tobacco smoke, Cd-contaminated food and industrial contamination are the main sources of Cd toxicity in humans (2,3).…”

Cadmium Sulfide Nanoparticles: Preparation, Characterization, and Biomedical Applications

“…The surface oxidation of the CdS NPs causes the release of cadmium ions from the CdS NPs into the cell medium [36]. To affect cancer cells and induce cell toxicity, CdS NPs cause oxidative stress, inhibit antioxidant function, exert genotoxic effects, affect calcium homeostasis in cells, and induce apoptosis [108]. In addition, CdS NPs generate ROS by electron-hole pairs to transfer electrons to oxygen, directly interact with the intracellular antioxidant system, or elevate the ROS molecules by releasing Cd 2+ ions [23].…”