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

Sebastiano Di Bucchianico,1 Maria Rita Fabbrizi,1 Silvia Cirillo,1 Chiara Uboldi,1 Douglas Gilliland,2 Eugenia Valsami-Jones,3,4 Lucia Migliore11Department of Translational Research and New Technologies in Medicine and Surgery, Medical Genetics Unit, University of Pisa, Pisa, Italy; 2European Commi...

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Autores principales:	Di Bucchianico S, Fabbrizi MR, Cirillo S, Uboldi C, Gillil, D, Valsami-Jones E, Migliore L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/425a80a0c1ae462da10e53e40a85f296
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spelling	oai:doaj.org-article:425a80a0c1ae462da10e53e40a85f2962021-12-02T03:54:16ZAneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles1178-2013https://doaj.org/article/425a80a0c1ae462da10e53e40a85f2962014-05-01T00:00:00Zhttp://www.dovepress.com/aneuploidogenic-effects-and-dna-oxidation-induced-in-vitro-by-differen-a16737https://doaj.org/toc/1178-2013 Sebastiano Di Bucchianico,1 Maria Rita Fabbrizi,1 Silvia Cirillo,1 Chiara Uboldi,1 Douglas Gilliland,2 Eugenia Valsami-Jones,3,4 Lucia Migliore11Department of Translational Research and New Technologies in Medicine and Surgery, Medical Genetics Unit, University of Pisa, Pisa, Italy; 2European Commission-Joint Research Centre, Institute for Health and Consumer Protection, NanoBioSciences Unit, Ispra, Italy; 3School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, UK; 4Earth Sciences, Natural History Museum, Cromwell Road, London, UKAbstract: 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.Keywords: Au nanoparticles, cytotoxicity, aneuploidy, oxidative DNA damage, micronuclei, particle sizeDi Bucchianico SFabbrizi MRCirillo SUboldi CGillilDValsami-Jones EMigliore LDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 2191-2204 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Di Bucchianico S Fabbrizi MR Cirillo S Uboldi C Gillil D Valsami-Jones E Migliore L Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles
description	Sebastiano Di Bucchianico,1 Maria Rita Fabbrizi,1 Silvia Cirillo,1 Chiara Uboldi,1 Douglas Gilliland,2 Eugenia Valsami-Jones,3,4 Lucia Migliore11Department of Translational Research and New Technologies in Medicine and Surgery, Medical Genetics Unit, University of Pisa, Pisa, Italy; 2European Commission-Joint Research Centre, Institute for Health and Consumer Protection, NanoBioSciences Unit, Ispra, Italy; 3School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, UK; 4Earth Sciences, Natural History Museum, Cromwell Road, London, UKAbstract: 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.Keywords: Au nanoparticles, cytotoxicity, aneuploidy, oxidative DNA damage, micronuclei, particle size
format	article
author	Di Bucchianico S Fabbrizi MR Cirillo S Uboldi C Gillil D Valsami-Jones E Migliore L
author_facet	Di Bucchianico S Fabbrizi MR Cirillo S Uboldi C Gillil D Valsami-Jones E Migliore L
author_sort	Di Bucchianico S
title	Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles
title_short	Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles
title_full	Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles
title_fullStr	Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles
title_full_unstemmed	Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles
title_sort	aneuploidogenic effects and dna oxidation induced in vitro by differently sized gold nanoparticles
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/425a80a0c1ae462da10e53e40a85f296
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Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles

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