1. Zinc oxide nanoparticles induced gene mutation at the HGPRT locus and cell cycle arrest associated with apoptosis in V-79 cells
- Author
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Kavita Dubey, Divya Singh, Abhishek Kumar Jain, Renuka Maurya, and Alok K. Pandey
- Subjects
Hypoxanthine Phosphoribosyltransferase ,DNA damage ,Surface Properties ,Apoptosis ,010501 environmental sciences ,Gene mutation ,Toxicology ,medicine.disease_cause ,01 natural sciences ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Cricetulus ,medicine ,Animals ,Propidium iodide ,Particle Size ,030304 developmental biology ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,0303 health sciences ,Reactive oxygen species ,Micronucleus Tests ,Chemistry ,Cell Cycle ,Cell cycle ,Fibroblasts ,Molecular biology ,Comet assay ,Mutation ,Nanoparticles ,Comet Assay ,Zinc Oxide ,Genotoxicity ,Oxidative stress ,DNA Damage - Abstract
In recent years, the large-scale production of ZnO nanoparticles (NPs) for various applications is increasing exponentially and may pose serious health issues when inhaled either during occupational exposure or in consumer settings. The mechanisms underlying the toxicity of NPs have recently been studied intensively. Despite the existing studies, the mutagenicity of ZnO NPs in the eukaryotic system is still unclear. Therefore, the aim of the present study was to investigate the mutagenic potential of ZnO NPs using Chinese hamster lung fibroblast cells (V-79) as an in-vitro model. The study has demonstrated a significant uptake of ZnO NPs by flow cytometry with the confirmation of transmission electron microscopy. A reduction in cell viability was observed with a concomitant increase in reactive oxygen species (**P < 0.01, ***P < 0.001) after ZnO NP (1-20 μg/mL) exposure. Excessive reactive oxygen species can induce oxidative stress, which leads to genotoxic insult, and further gene mutation. Apart from measuring the genotoxicity by Comet assay, a change of 2.84-fold in the HGPRT gene mutant frequency was observed by the mammalian gene forward mutation assay. All the genotoxicity endpoints such as chromosomal break, DNA damage and mutagenicity were observed at 6 hours of ZnO NP exposure. Our results also showed that ZnO NPs manifested the cell cycle arrest, ultrastructural modifications and further cell death. A significant (**P < 0.01, ***P < 0.001) increase in the apoptotic cells was detected using annexin V-fluorescein isothiocyanate/propidium iodide double staining by flow cytometry. Our findings presented here clearly stimulate the need for careful regulations of ZnO NPs.
- Published
- 2018