Direct and Indirect Genotoxicity of Graphene Family Nanomaterials on DNA—A Review

Abstract

Graphene family nanomaterials (GFNs), including graphene, graphene oxide (GO), reduced graphene oxide (rGO), and graphene quantum dots (GQDs), have manifold potential applications, leading to the possibility of their release into environments and the exposure to humans and other organisms. However, the genotoxicity of GFNs on DNA remains largely unknown. In this review, we highlight the interactions between DNA and GFNs and summarize the mechanisms of genotoxicity induced by GFNs. Generally, the genotoxicity can be sub-classified into direct genotoxicity and indirect genotoxicity. The direct genotoxicity (e.g., direct physical nucleus and DNA damage) and indirect genotoxicity mechanisms (e.g., physical destruction, oxidative stress, epigenetic toxicity, and DNA replication) of GFNs were summarized in the manuscript, respectively. Moreover, the influences factors, such as physicochemical properties, exposure dose, and time, on the genotoxicity of GFNs are also briefly discussed. Given the important role of genotoxicity in GFNs exposure risk assessment, future research should be conducted on the following: (1) developing reliable testing methods; (2) elucidating the response mechanisms associated with genotoxicity in depth; and (3) enriching the evaluation database regarding the type of GFNs, applied dosages, and exposure times.

Bioactivity of PEGylated Graphene Oxide Nanoparticles Combined with Near-Infrared Laser Irradiation Studied in Colorectal Carcinoma Cells

“…Previous studies have also shown that exposure to graphene oxide and rGONR-PEG caused concentration and size-dependent DNA damage in different cancer cells including human ovarian cancer cells, human Glioblastoma multiforme cells (GBMU87), human alveolar adenocarcinoma cells (A549), CaCO2 and Vero cell lines [51,[60][61][62][63], suggesting that GO and GO-PEG have genotoxic effects on cells, depending on their nature and treatment protocols. These results signified that the cyto-and genotoxicity of graphene materials should be carefully studied before combining with the other therapeutic approaches such as photothermal therapy [64]. Our studies demonstrated that PEGylation of GO alone and in combination with NIR had none to little DNA damaging activity in Colon26 and HT29 cells, respectively, after 24 h of cultivation and higher genotoxicity after 72 h of cultivation.…”

Genotoxicity of Graphene-Based Materials

“…As previously mentioned, DNA damage induced by oxidative stress is a well-established mechanism of action of GBMs [ 29 ]; however, GO (and also GNPs) reported positive results in the standard comet assay but negative ones in the Fpg-modified comet assay [ 70 ].…”

“…As in the case of other nanomaterials, oxidative stress mediated by ROS generation is one of the main indirect mechanisms of GBMs’ genotoxicity [ 29 ]. For instance, ROS-dependent DNA damage (detected by the comet assay) was observed in human retinal pigment epithelium ARPE-19 cells after 24 h exposure to GO and rGO [ 68 ].…”

“…GBMs, similar to other nanomaterials, could be genotoxic through primary or secondary mechanisms of action [ 29 ] ( Figure 2 ). Primary genotoxicity could be induced by direct interaction of the material with the DNA molecule or its associated histones, or indirectly, by interfering with DNA replication or repair through the induction of lipid peroxidation, or by triggering the formation of reactive oxygen species (ROS).…”

Special Issue “The Genetic Changes Induced by Engineered Manufactured Nanomaterials (EMNs)”

“…As explained in one of the reviews included in this Special Issue, the number and quantity of nanomaterials is ever increasing and affecting the environment where humans, bacteria, and plants live, and their genome come in contact with nanomaterials [3]. Although the topic of genotoxicity induced by nanomaterials is important, we had only five contributions for this Special Issue: [3][4][5][6][7][8]. Marmiroli et al, 2022 [3], contributed a minireview on the methods used to analyze genotoxicity in plants.…”