Graphene oxide can induce in vitro and in vivo mutagenesis
Yuanyuan Liu1, Yi Luo, Jing Wu
1Research Center of Basic Medical Science & School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China.
Abstract:
Graphene oxide (GO) has attracted enormous interests due to its extraordinary properties. Recent studies have confirmed the cytotoxicity of GO, we further investigate its mutagenic potential in this study. The results showed that GO interfered with DNA replication and induced mutagenesis at molecular level. GO treatments at concentrations of 10 and 100 μg/mL altered gene expression patterns at cellular level, and 101 differentially expressed genes mediated DNA-damage control, cell apoptosis, cell cycle, and metabolism. Intravenous injection of GO at 4 mg/kg for 5 consecutive days clearly induced formation of micronucleated polychromic erythrocytes in mice, and its mutagenesis potential appeared to be comparable to cyclophosphamide, a classic mutagen. In conclusion, GO can induce mutagenesis both in vitro and in vivo, thus extra consideration is required for its biomedical applications.
Insights
Graphene oxide (GO) can damage DNA and cause mutations in cells and living organisms. Further research is needed before its use in biomedical applications due to its mutagenic potential.
Area of Science:
- Nanomaterials Science
- Toxicology
- Molecular Biology
Background:
- Graphene oxide (GO) exhibits remarkable properties, driving significant research interest.
- Previous studies have established the cytotoxicity of GO.
- This study investigates the mutagenic potential of GO, a critical aspect for its safe application.
Purpose of the Study:
- To evaluate the mutagenic potential of graphene oxide (GO) at molecular, cellular, and in vivo levels.
- To understand the mechanisms by which GO may induce genetic damage.
- To assess the implications of GO's mutagenicity for its biomedical applications.
Main Methods:
- In vitro assays to assess DNA replication interference and mutagenesis.
- Gene expression profiling (RNA sequencing) to identify affected cellular pathways at 10 and 100 μg/mL GO concentrations.
- In vivo studies involving intravenous injection of GO in mice (4 mg/kg for 5 days) to assess mutagenicity via micronucleus tests.
- Comparison of GO's mutagenic potential with cyclophosphamide.
Main Results:
- Graphene oxide (GO) interferes with DNA replication and induces mutagenesis at the molecular level.
- GO treatment alters gene expression, affecting DNA-damage control, apoptosis, cell cycle, and metabolism, with 101 differentially expressed genes identified.
- In vivo studies demonstrated that GO induces the formation of micronucleated polychromic erythrocytes in mice.
- The mutagenic potential of GO in vivo was found to be comparable to cyclophosphamide.
Conclusions:
- Graphene oxide (GO) possesses mutagenic potential, confirmed through both in vitro and in vivo experiments.
- GO's ability to induce genetic alterations necessitates careful consideration for its use in biomedical applications.
- Further safety assessments are crucial before widespread adoption of GO in medicine.
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