Mutation Research 751–752 (2013) 42–48 Contents lists available at ScienceDirect Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis journa l ho me p ag e: www.elsevier.com/locate/molmut Co mm u nit y add ress: www.elsevier.com/locate/mutres Transplacental clastogenic and epigenetic effects of gold nanoparticles in mice Roumen Balansky a , Mariagrazia Longobardi b , Gancho Ganchev a , Marietta Iltcheva a , Nikolay Nedyalkov c , Petar Atanasov c , Reneta Toshkova d , Silvio De Flora b , Alberto Izzotti b,∗ a National Center of Oncology, Sofia, Bulgaria b Department of Health Sciences, University of Genoa, Genoa, Italy c Institute of Electronics, Bulgarian Academy of Sciences, Sofia, Bulgaria d Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria a r t i c l e i n f o Article history: Received 22 March 2013 Received in revised form 1 August 2013 Accepted 23 August 2013 Available online 1 September 2013 Keywords: Gold nanoparticles Transplacental Mouse fetus Clastogenicity microRNA expression a b s t r a c t The broad application of nanotechnology in medicine, biology, and pharmacology is leading to a dramatic increase of the risk of direct contact of nanoproducts, among which gold nanoparticles (AuNP), with the human organism. The present study aimed at evaluating in vivo the genotoxicity of AuNPs with average size of 40 nm and 100 nm. A single intraperitoneal treatment of adult male and female Swiss mice (strain H) with AuNPs, at a dose of 3.3 mg/kg body weight, had no effect on the frequency of micronucleated polychromatic erythrocytes (MN PCEs) in bone marrow. Conversely, the transplacental treatment with AuNP-100 nm, but not with AuNP-40 nm, applied intraperitoneally at a dose of 3.3 mg/kg to pregnant mice on days 10, 12, 14, and 17 of gestation, resulted in a significant increase in the frequency of MN PCEs in both liver and peripheral blood of mouse fetuses. In parallel, the same treatment with AuNP-100 nm, but not with AuNP-40 nm, produced significant changes in microRNA expression. In particular, out of 1281 mouse microRNAs analyzed, 28 were dys-regulated more than two-fold and to a statistically significant extent in fetus lung, and 5 were up-regulated in fetal liver. Let-7a and miR-183 were significantly up-regulated in both organs. The data presented herein demonstrate for the first time the transplacental size-dependent clastogenic and epigenetic effects of AuNPs in mouse fetus, thus highlighting new aspects concerning the putative genotoxicity of AuNPs during a vulnerable period of life. © 2013 Elsevier B.V. All rights reserved. 1. Introduction The field of nanotechnology has become one of the most inten- sively growing areas of research. A wide spectrum of nanomaterials have been manufactured and used not only in industry but also in medicine, biology, pharmacology, and daily human life. A number of nanoparticles (NPs) are already in use or under investigation for their possible applications as drug and gene carriers and for the production of biocompatible materials as well as for medical mon- itoring, in vitro and in vivo diagnostics, and therapy of neoplastic diseases [1–4]. The increasing manufacturing and wide distribu- tion of nanomaterials in human life may involve opportunities for direct contact with the human organism. Therefore, the resulting Abbreviations: AuNPs, gold nanoparticles; miRNAs, microRNAs; MN, micronucleated; NP, nanoparticles; PCEs, polychromatic erythrocytes; NCEs, normochromatic erythrocytes. ∗ Corresponding author. Tel.: +39 010 3538522; fax: +39 010 3538504. E-mail address: izzotti@unige.it (A. Izzotti). potential risk should be carefully evaluated in order to prove the safety of NPs. The possible health hazard of NPs is mainly linked to their size, chemical composition and structure, shape, and surface charge. In particular, the particle size is a key feature defining their bio- logical activity [5]. In most cases, smaller nanoparticles produce greater biological responses compared to their larger counterparts, due to differences in the surface/volume ratio. Despite the fact that nanotoxicology and nanogenotoxicology are newly emerging sci- entific disciplines, the data accumulated during the last years have clearly indicated that nanomaterials may possess toxic and geno- toxic properties. For example, Landsiedel et al. [6] reported that, in 14 of 19 studies using the comet assay and in 12 of 14 studies using the micronucleus test, positive results were obtained by testing a variety of NPs, such as engineered TiO 2 , cobalt chrome, ZnO, SiO 2 , Fe(II) and (III), carbon nanotubes, and carbon black. Special attention should be paid to gold nanoparticles (AuNPs), due to their potential medical applications, such as plasmon- based labeling and imaging, optical and electrochemical sensing, diagnostics and therapy for a number of diseases, including 0027-5107/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.mrfmmm.2013.08.006