Research Article Palladium Nanoparticles Induce Disturbances in Cell Cycle Entry and Progression of Peripheral Blood Mononuclear Cells: Paramount Role of Ions Claudia Petrarca, 1 Emanuela Clemente, 2 Luca Di Giampaolo, 2 Renato Mariani-Costantini, 3 Kerstin Leopold, 4 Roland Schindl, 4 Lavinia V. Lotti, 5 Rocco Mangifesta, 1 Enrico Sabbioni, 1 Qiao Niu, 6 Giovanni Bernardini, 7,8 and Mario Di Gioacchino 1,2 1 Immunotoxicology and Allergy Unit, Ce.S.I., “G. d’Annunzio” University Foundation, 66100 Chieti, Italy 2 Department of Medicine and Ageing Science, “G. d’Annunzio” University, 66100 Chieti, Italy 3 Unit of General Pathology, Ce.S.I., “G. d’Annunzio” University Foundation and Department of Medicine, Dentistry and Biotechnology, G. d’Annunzio University, 66100 Chieti, Italy 4 University of Ulm, Institute for Analytical and Bioanalytical Chemistry, 89081 Ulm, Germany 5 Laboratorio di Biopatologia Ultrastrutturale, Department of Experimental Medicine, University of Rome “La Sapienza”, 00161 Rome, Italy 6 Shanxi Medical University, Taiyuan, China 7 Department of Biotechnology and Molecular Sciences, University of Insubria, 21100 Varese, Italy 8 he Protein Factory, Interuniversity Centre Politecnico di Milano, ICRM CNR Milano and University of Insubria, 20131 Milan, Italy Correspondence should be addressed to Claudia Petrarca; c.petrarca@unich.it Received 5 March 2014; Revised 6 June 2014; Accepted 8 June 2014; Published 3 July 2014 Academic Editor: Andrij Holian Copyright © 2014 Claudia Petrarca et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. here is concern about the possible toxicity of palladium nanoparticles (Pd-NP), as they are released in the environment through many applications. We previously studied the toxicity of Pd-NP at high concentrations; here we address the possible toxicity of Pd-NP at low, subtoxic doses. In particular, we have exposed normal human PBMC entering into the irst in vitro mitotic division to Pd-NP and to Pd(IV) ions to evaluate ROS generation and cell cycle progression. We have measured a statistically signiicant increase of intracellular ROS in Pd(IV) exposed cells, but not in Pd-NP exposed cells. TEM revealed accumulation of lipid droplets and autophagic and mitophagic vacuoles, which appeared more conspicuous in cells exposed to Pd(IV) ions than to Pd-NP. Pd-NP were visible in the cytoplasm of Pd-NP exposed cells. Pd-NP addition was associated with a signiicant increase of cells within the G0/G1-phase and a signiicant reduction in GS- and G2/M-phases. Cells exposed to Pd(IV) ions showed a signiicant ampliication of these cell cycle alterations. hese results suggest that ions, per se or released by NPs, are the true inducers of Pd toxicity. It will be essential to verify whether the observed disturbance represents a temporary response or might result in permanent alterations. 1. Introduction Palladium (Pd) is a component of the catalytic converters that promotes reduction and oxidation of pollutants in exhaust gases to less harmful ones [1]. Catalytic converters emit Pd mainly as particulate matter in the breathable size range (< 2.5 m) [2, 3], containing also Pd-NP ( < 100 nm) [4]. Indeed, ater the introduction of catalytic converters based on the Pt group elements, the level of Pd (also in the form of nanoparticles) rapidly increased in the areas bordering roads [5–10]. At the same time, in Europe, allergic sensitization to Pd increased [11–14]. A causative role for Pd(II) ions in the development of allergic symptoms has been deduced from studies on occupationally exposed people [14–16] and people Hindawi Publishing Corporation Journal of Immunology Research Volume 2014, Article ID 295092, 8 pages http://dx.doi.org/10.1155/2014/295092