Transient DNA damage following exposure to gold nanoparticles

Abstract

Due to their interesting physicochemical properties, gold nanoparticles (Au-NPs) are the focus of increasing attention in the field of biomedicine and are under consideration for use in drug delivery and bioimaging, or as radiosensitizers and nano-based vaccines. Thorough evaluation of the genotoxic potential of Au-NPs is required, since damage to the genome can remain undetected in standard hazard assessments. Available genotoxicity data is either limited or contradictory. Here, we examined the influence of three surface modified 3-4 nm Au-NPs on human A549 cells, according to the reactive oxygen species (ROS) paradigm. After 24 h of Au-NP treatment, nanoparticles were taken up by cells as agglomerates; however, no influence on cell viability or inflammation was detected. No increase in ROS production was observed by H2-DCF assay; however, intracellular glutathione levels reduced over time, indicating oxidative stress. All three types of Au-NPs induced DNA damage, as detected by alkaline comet assay. The strongest genotoxic effect was observed for positively charged Au-NP I. Further analysis of Au-NP I by neutral comet assay, fluorimetric detection of alkaline DNA unwinding assay, and γH2AX staining, revealed that the induced DNA lesions were predominantly alkali-labile sites. As highly controlled repair mechanisms have evolved to remove a wide range of DNA lesions with great efficiency, it is important to focus on both acute cyto- and genotoxicity, alongside post-treatment effects and DNA repair. We demonstrate that Au-NP-induced DNA damage is largely repaired over time, indicating that the observed damage is of transient nature.

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“…[38][39][40] In recent years, exposure to gold nanoparticles has been reported to cause transient DNA damage due to the generation of alkali-labile sites and oxidative stress with a decrease in glutathione. 41,42 However, the phosphorylation level of H2A.X showed no change after treatment with U2-AuNP 24 hr. We considered that this phenomenon might be caused by a long U2-AuNP treatment time since DNA double-strand breaks (DSBs) happen within several hours.…”

Megavoltage Radiosensitization of Gold Nanoparticles on a Glioblastoma Cancer Cell Line Using a Clinical Platform

“…The rationale behind utilizing 42 nm GNP in this experiment was based on a study by Chitrani's group that demonstrated 50 nm GNPs exhibited the highest radiosensitization in HeLa cells compared to 14 and 74 nm GNPs when irradiated with 220 kVp X-rays; DEF of 1.43 compared to 1.2 and 1.25, respectively [21]. In addition, various reports have shown the relative safety of GNPs in the range of 20-50 nm in different cell lines [22,23]. A recent in vitro study demonstrated no GNP-associated toxicity on HepG2 cells when incubated with 20 and 50 nm GNPs [24].…”

An automatable platform for genotoxicity testing of nanomaterials based on the fluorometric γ-H2AX assay reveals no genotoxicity of properly surface-shielded cadmium-based quantum dots

“…79 The controversial findings for the genotoxicity of Au-NPs may be due to the fact that a repair of DNA damage may also occur after Au-NP exposure. 80 We can only speculate on the mechanism of the genotoxicity induced by the 30 nm-sized AuNPs in this study. Although our 30 nm-sized citrate-stabilized Au NPs are too large to penetrate the nucleus, they may nevertheless be able to generate ROS in the cytoplasm which could then induce oxidative damage in the nucleus.…”