Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles

• Published in: International journal of nanomedicine Vol. 9; no. Issue 1; pp. 2191 - 2204
• Main Authors: Di Bucchianico, Sebastiano, Fabbrizi, Maria Rita, Cirillo, Silvia, Uboldi, Chiara, Gilliland, Douglas, Valsami-Jones, Eugenia, Migliore, Lucia
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2014; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Aneugens - pharmacology; Aneuploidy; Animals; Au nanoparticles; Biomedical materials; Biotechnology; Cellular Biology; Chromosome Aberrations - chemically induced; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - physiology; DNA methylation; Epigenetics; Fibroblasts; Gene expression; Genetic aspects; Genetics; Gold; Gold - pharmacology; Humans; Life Sciences; Macrophages - drug effects; Macrophages - physiology; Materials Testing; Metal Nanoparticles - administration & dosage; Mice; micronuclei; Nanoparticles; Original Research; Oxidation-Reduction - drug effects; oxidative DNA damage; Particle Size; Physiological aspects; Proteins; Surface chemistry; Toxicology; Italy; United Kingdom > UK; Netherlands; aneuploidy; particle size; Au nanoparticles; micronuclei; oxidative DNA damage; cytotoxicity
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/ijn.s58397

Gold nanoparticles (Au NPs) are used in many fields, including biomedical applications; however, no conclusive information on their potential cytotoxicity and genotoxicity mechanisms is available. For this reason, experiments in human primary lymphocytes and murine macrophages (Raw264.7) were performed exposing cells to spherical citrate-capped Au NPs with two different nominal diameters (5 nm and 15 nm). The proliferative activity, mitotic, apoptotic, and necrotic markers, as well as chromosomal damage were assessed by the cytokinesis-block micronucleus cytome assay. Fluorescence in situ hybridization with human and murine pancentromeric probes was applied to distinguish between clastogenic and aneuploidogenic effects. Our results indicate that 5 nm and 15 nm Au NPs are able to inhibit cell proliferation by apoptosis and to induce chromosomal damage, in particular chromosome mis-segregation. DNA strand breaks were detected by comet assay, and the modified protocol using endonuclease-III and formamidopyrimidine-DNA glycosylase restriction enzymes showed that pyrimidines and purines were oxidatively damaged by Au NPs. Moreover, we show a size-independent correlation between the cytotoxicity of Au NPs and their tested mass concentration or absolute number, and genotoxic effects which were more severe for Au NP 15 nm compared to Au NP 5 nm. Results indicate that apoptosis, aneuploidy, and DNA oxidation play a pivotal role in the cytotoxicity and genotoxicity exerted by Au NPs in our cell models.