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.
Currently, GFNs, as promising nanomaterials, have attracted increasing attention in the scientific community and are in commercial production for many applications, such as energy storage , medicine , environmental protection , and industrial manufacturing . For example, the market for graphene-based products is forecast to reach $675 million by 2020 . With rapid developments in application and production of GFNs, their potential for release into the environment and the environmental risks of GFNs have become emerging issues . Consequently, many studies have shown that adverse effects can be induced by GFNs in vivo and in vitro, such as organ (e.g., lung, liver, and spleen) toxicity, cytotoxicity, immunotoxicity, neurotoxicity, and reproductive and developmental toxicity . Moreover, the toxicity mechanisms of GFNs to organisms, including physical destruction, oxidative stress, inflammatory response, apoptosis, autophagy, and necrosis, are summarized in Table 1 . However, the genotoxicity of GFNs on DNA (e.g., DNA damage) remains largely unknown.
|Products||Supplier or Synthesis Methods||Dose||Animal or Cell Models||Toxicological Mechanisms||Adverse Effects||Ref.|
|graphene nanoplatelets||cheaptubes.com (Brattleboro, VT, USA)||0.3, 1 mg/rat||rat||oxidative stress, inflammation||lung inflammation|||
|commercial GO and rGO||Nanjing XFNANO Materials Tech Co., Ltd., (China)||2.0 mg/kg body weight||rat||transcriptional and epigenetic||liver zonated accumulation|||
|Nanjing XFNANO Materials Tech Co., Ltd., (China)||100, 200 μg/mL||A549 cells||autophagy||cytotoxicity|||
|GO and rGO oxidated from carbon nanofibers||Grupo Antolin
|0.1, 1.0, 10, 50 mg/L||erythrocyte cell||oxidative stress||genotoxicity|||
|GO nanosheets||Sigma-Aldrich (St. Louis, MO, USA)||40, 60, 80 mg/L||Human SH-SY5Y neuroblastoma cell||oxidative stress, autophagy–lysosomal network dysfunction||cytotoxicity|||
|pristine rGO||Chengdu Organic Chemicals Co., Ltd., the Chinese Academy of Sciences||1–100 mg/L||Earthworm coelomocytes||oxidative stress||immunotoxicity|||
|single layer GO
(product no. GNOP10A5)
|ACS Materials LLC (Medford, MA, USA)||1, 10, 50, 150, 250, 500 mg/L||Escherichia coli||physical destruction||toxicity against bacteria|||
|GO||modified Hummers method||25 mg/L||THP-1 and BEAS-2B cells||lipid peroxidation, membrane adsorption, membrane damage||cytotoxicity|||
|GO||modified Hummers method||2 mg/kg||rat||lipid peroxidation, membrane adsorption, membrane damage||acute lung inflammation|||
|GO||Nanjing XFNANO Materials Tech Co., Ltd., (China)||0–100 mg/L||zebrafish embryos||oxidative stress||developmental toxicity|||
|GO||modified Hummers method||10 mg/L||Caenorhabditis elegans||oxidative stress||toxicity|||
|modified Hummers method||3.125–200 mg/L||human erythrocytes and skin fibroblasts||oxidative stress||cytotoxicity|||
|graphene exfoliated form graphite,
GO oxidated from carbon fibers
|Grupo Antolin Ingeniería (Burgos, Spain)||1, 10 mg/L||primary neurons||inhibition of synaptic transmission, altered calcium homeostasis||neurotoxicity|||
Genotoxicity is broadly defined as ‘damage to the genome’ and also a distinct and important type of toxicity, as specific genotoxic events are considered hallmarks of cancer . Generally, the genotoxicity can be sub-classified into direct genotoxicity and indirect genotoxicity in cells or the nucleus . Nanoparticles (NPs) can be uptaken by the nucleus and induce DNA damage, leading to direct genotoxicity on organisms . While many studies have shown that most NPs cannot enter the nucleus, they still indirectly affect genotoxicity by oxidative stress, epigenetic changes, inflammation, and autophagy . Moreover, genotoxicity plays a key role in assessing the safety of NPs on human health and the environment . Although there has been many researches about the genotoxicity of NPs in recent years, it is mainly focused on traditional artificial nanomaterials, such as TiO 2, carbon nanotubes, and silver and gold NPs . However, the existing literature on genotoxicity of GFNs remains limited and conflicting. A few studies showed that GFNs had no adverse effects on genotoxicity . In contrast, many researchers have reported that the small size and sharp edges of GFNs (e.g., GO and GQDs) can induce genotoxicity on aquatic organisms (e.g., fish and algae) . However, the direct and indirect genotoxicity mechanisms of GFNs remain unclear, despite genotoxic phenomena being widely reported.