title: Palladium nanoparticles induce disturbances in cell cycle entry and progression of peripheral blood mononuclear cells: paramount role of ions.
abstract: There 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 first 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 significant 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 significant increase of cells within the G0/G1-phase and a significant reduction in GS- and G2/M-phases. Cells exposed to Pd(IV) ions showed a significant amplification of these cell cycle alterations. These 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.
authors.affiliation: Immunotoxicology and Allergy Unit, Ce.S.I., "G. d'Annunzio" University Foundation, 66100 Chieti, Italy.
authors.forename: Claudia
authors.identifier: 0000-0002-6910-0160
authors.initials: C
authors.lastname: Petrarca
authors.affiliation: Department of Medicine and Ageing Science, "G. d'Annunzio" University, 66100 Chieti, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Clemente
authors.affiliation: Department of Medicine and Ageing Science, "G. d'Annunzio" University, 66100 Chieti, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Di Giampaolo
authors.affiliation: 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.
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
authors.affiliation: University of Ulm, Institute for Analytical and Bioanalytical Chemistry, 89081 Ulm, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Leopold
authors.affiliation: University of Ulm, Institute for Analytical and Bioanalytical Chemistry, 89081 Ulm, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schindl
authors.affiliation: Laboratorio di Biopatologia Ultrastrutturale, Department of Experimental Medicine, University of Rome "La Sapienza", 00161 Rome, Italy.
authors.forename: Lavinia V
authors.initials: LV
authors.lastname: Lotti
authors.affiliation: Immunotoxicology and Allergy Unit, Ce.S.I., "G. d'Annunzio" University Foundation, 66100 Chieti, Italy.
authors.forename: Rocco
authors.identifier: 0000-0003-4663-7165
authors.initials: R
authors.lastname: Mangifesta
authors.affiliation: Immunotoxicology and Allergy Unit, Ce.S.I., "G. d'Annunzio" University Foundation, 66100 Chieti, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Sabbioni
authors.affiliation: Shanxi Medical University, Taiyuan, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Niu
authors.affiliation: Department of Biotechnology and Molecular Sciences, University of Insubria, 21100 Varese, Italy ; The Protein Factory, Interuniversity Centre Politecnico di Milano, ICRM CNR Milano and University of Insubria, 20131 Milan, Italy.
authors.forename: Giovanni
authors.identifier: 0000-0002-3545-0103
authors.initials: G
authors.lastname: Bernardini
authors.affiliation: Immunotoxicology and Allergy Unit, Ce.S.I., "G. d'Annunzio" University Foundation, 66100 Chieti, Italy ; Department of Medicine and Ageing Science, "G. d'Annunzio" University, 66100 Chieti, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Di Gioacchino
mesh_terms: D002453:Cell Cycle / Q000187:drug effects*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007477:Ions / Q000008:administration & dosage / Q000633:toxicity; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D053758:Nanoparticles; D010165:Palladium / Q000008:administration & dosage* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007477:Ions; D017382:Reactive Oxygen Species; D010165:Palladium
references.citation: Nat Rev Cancer. 2009 Mar;9(3):153-66
references.pmid: 19238148
references.citation: Sci Total Environ. 2008 Mar 15;392(1):50-8
references.pmid: 18166216
references.citation: Cell Res. 2000 Mar;10(1):1-16
references.pmid: 10765979
references.citation: Pediatr Dermatol. 2003 Mar-Apr;20(2):119-23
references.pmid: 12657006
references.citation: Free Radic Res. 2010 May;44(5):479-96
references.pmid: 20370557
references.citation: Ecotoxicology. 2002 Oct;11(5):385-92
references.pmid: 12463686
references.citation: J Biol Regul Homeost Agents. 2010 Apr-Jun;24(2):207-14
references.pmid: 20487634
references.citation: Prog Cell Cycle Res. 2003;5:5-18
references.pmid: 14593696
references.citation: Nanotoxicology. 2014 Jun;8(4):455-64
references.pmid: 23586465
references.citation: Mutagenesis. 2002 Sep;17(5):411-7
references.pmid: 12202629
references.citation: Int J Hyg Environ Health. 2002 Oct;205(6):417-32
references.pmid: 12455264
references.citation: Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):605-14
references.pmid: 19822077
references.citation: Clin Exp Immunol. 2006 Dec;146(3):417-26
references.pmid: 17100760
references.citation: Int J Immunopathol Pharmacol. 2006 Oct-Dec;19(4 Suppl):21-4
references.pmid: 17291402
references.citation: Environ Sci Technol. 2007 Jan 15;41(2):451-6
references.pmid: 17310706
references.citation: Cell Cycle. 2007 Sep 15;6(18):2263-7
references.pmid: 17890908
references.citation: Sci Total Environ. 2008 May 1;394(1):177-82
references.pmid: 18279916
references.citation: Biochem J. 2012 Jan 15;441(2):523-40
references.pmid: 22187934
references.citation: Contact Dermatitis. 1997 Dec;37(6):286-93
references.pmid: 9455632
references.citation: Autophagy. 2008 May;4(4):537-9
references.pmid: 18398291
references.citation: Int J Cell Biol. 2012;2012:219625
references.pmid: 22666256
references.citation: Int J Oncol. 2007 May;30(5):1051-8
references.pmid: 17390006
references.citation: Environ Res. 2005 Jun;98(2):203-9
references.pmid: 15820726
references.citation: Environ Sci Technol. 2012 Mar 20;46(6):3149-54
references.pmid: 22313190
references.citation: Sci Total Environ. 2003 Dec 30;317(1-3):121-35
references.pmid: 14630416
references.citation: Am J Contact Dermat. 2003 Jun;14(2):78-81
references.pmid: 14749025
references.citation: Oncogene. 2013 Aug 15;32(33):3789-97
references.pmid: 23208502
references.citation: Contact Dermatitis. 2000 Dec;43(6):333-8
references.pmid: 11140383
references.citation: J Biol Regul Homeost Agents. 2013 Apr-Jun;27(2):443-54
references.pmid: 23830394
references.citation: Nanotoxicology. 2014 Feb;8(1):88-99
references.pmid: 23167736
references.citation: Environ Pollut. 2008 Nov;156(2):341-7
references.pmid: 18355951
references.citation: Int J Immunopathol Pharmacol. 2007 Apr-Jun;20(2 Suppl 2):15-22
references.pmid: 17903351
references.citation: Environ Sci Process Impacts. 2013 Jan;15(1):39-48
references.pmid: 24592426
references.citation: Nat Chem. 2011 Mar;3(3):239-43
references.pmid: 21336331
references.citation: Circ Res. 2012 Oct 12;111(9):1208-21
references.pmid: 23065344
references.citation: Ann Clin Lab Sci. 2004 Summer;34(3):299-306
references.pmid: 15487704
references.citation: Occup Environ Med. 1999 Mar;56(3):191-6
references.pmid: 10448328
references.citation: Sci Total Environ. 2001 Apr 10;270(1-3):165-73
references.pmid: 11327390
references.citation: Allergy. 2009 Aug;64(8):1152-6
references.pmid: 19208086