title: Transplacental clastogenic and epigenetic effects of gold nanoparticles in mice.
abstract: 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.
authors.affiliation: National Center of Oncology, Sofia, Bulgaria.
authors.forename: Roumen
authors.initials: R
authors.lastname: Balansky
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Longobardi
authors.forename: Gancho
authors.initials: G
authors.lastname: Ganchev
authors.forename: Marietta
authors.initials: M
authors.lastname: Iltcheva
authors.forename: Nikolay
authors.initials: N
authors.lastname: Nedyalkov
authors.forename: Petar
authors.initials: P
authors.lastname: Atanasov
authors.forename: Reneta
authors.initials: R
authors.lastname: Toshkova
authors.forename: Silvio
authors.initials: S
authors.lastname: De Flora
authors.forename: Alberto
authors.initials: A
authors.lastname: Izzotti
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006046:Gold / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000196:embryology; D008168:Lung / Q000187:drug effects / Q000196:embryology; D051379:Mice; D035683:MicroRNAs; D015162:Micronucleus Tests; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000494:pharmacology*; D053758:Nanoparticles / Q000009:adverse effects*; D011247:Pregnancy
chemical_list: D035683:MicroRNAs; D009153:Mutagens; D006046:Gold
keywords: AuNPs; Clastogenicity; Gold nanoparticles; MN; Mouse fetus; NCEs; NP; PCEs; Transplacental; gold nanoparticles; miRNAs; microRNA expression; microRNAs; micronucleated; nanoparticles; normochromatic erythrocytes; polychromatic erythrocytes