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Mechanism of graphene‐induced cytotoxicity: Role of endonucleases
Author(s) -
Fahmi Tariq,
Branch La Donna,
Nima Zeid A.,
Jang Dae Song,
Savenka Alena V.,
Biris Alexandru S.,
Basnakian Alexei G.
Publication year - 2017
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3462
Subject(s) - tunel assay , dna fragmentation , endonuclease , microbiology and biotechnology , apoptosis , programmed cell death , apoptotic dna fragmentation , terminal deoxynucleotidyl transferase , fragmentation (computing) , chemistry , dna damage , deoxyribonuclease i , biology , biochemistry , dna , ecology , base sequence
Graphene, a crystalline allotrope or carbon, presents numerous useful properties; however, its toxicity is yet to be determined. One of the most dramatic and irreversible toxic abilities of carbon nanomaterials is the induction of DNA fragmentation produced by endogenous cellular endonucleases. This study demonstrated that pristine graphene exposed to cultured kidney tubular epithelial cells is capable of inducing DNA fragmentation measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, which is usually associated with cell death. TUNEL (cell death) and endonuclease activity measured using a near infrared fluorescence probe was significantly higher in cells containing graphene aggregates detected by Raman spectroscopy. The elevation of TUNEL coincided with the increased abundance of heme oxygenase 1 (HO‐1), heat shock protein 90 (HSP90), active caspase‐3 and endonucleases (deoxyribonuclease I [DNase I] and endonuclease G [EndoG]), as measured by quantitative immunocytochemistry. Specific inhibitors for HO‐1, HSP90, caspase‐3, DNase I and EndoG almost completely blocked the DNA fragmentation induced by graphene exposure. Therefore, graphene induces cell death through oxidative injury, caspase‐mediated and caspase‐independent pathways; and endonucleases DNase I and EndoG are important for graphene toxicity. Inhibition of these pathways may ameliorate cell injury produced by graphene. Copyright © 2017 John Wiley & Sons, Ltd.