In vivo genotoxicity and inflammatory effects of uncoated and coated CeO2 NPs in mice
Aimonen, K. ; Catalan, J. ; Suhonen, S. ; Hartikainen, M. ; Vippola, M. ; Moreno, C. (Universidad de Zaragoza) ; Cabellos, J. ; Janer, G. ; Campos, S.V. ; Wolff, H. ; Savolainen, K. ; Norppa, H.
Resumen: P17-045
Ceria nanoparticles (CeO2 NPs) have several industrial applications and pharmacological potential due to their antioxidant properties. However, toxicity data on CeO2 NPs are scarce and show contradictory results. In the present study, uncoated, polyethylene glycol- and citrate-coated CeO2 NPs (4-8 nm) were administrated to C57Bl/6 mice by repeated dose (3×) pharyngeal aspiration using four different doses of each type of NPs (corresponding to 4.4, 8.8, 17.6 and 35.2 µg Ce2+/mouse/aspiration), and sampled 1 and 28 days after the last administration. DNA damage was assessed by the comet assay locally in bronchoalveolar lavage (BAL) and lung cells, and systemically in liver cells. Micronuclei, a biomarker of chromosome damage, were analysed in bone marrow and peripheral blood erythrocytes. Immunotoxicity was evaluated by BAL cell counting. Furthermore, histopathological effects on the lungs and biodistribution of the NPs (analysis of Ce2+ in several organs) were assessed. At 24-h, a significant increase in DNA damage was induced at the highest doses by uncoated and citrate-coated NPs in BAL cells. For these NPs a significant, but non-dose-dependent, effect was observed in lung and liver cells at 28-d. No systemic genotoxic effects were observed with any of the NPs. A dose-dependent accumulation of macrophages and activated lymphocytes was seen in the lungs for all the NPs, although a milder reaction was elicited by the coated NPs. Our findings show that short-term exposure of mice to CeO2 NPs induces pulmonary inflammation, and non-dose-dependent DNA damage, but no systemic genotoxicity. (Funded by the EU FP-7 GUIDEnano, Grant Agreement No.604387).
Idioma: Inglés
DOI: 10.1016/j.toxlet.2016.06.1965
Año: 2016
Publicado en: TOXICOLOGY LETTERS 258, Suppl. (2016), S276 [P17-045]
ISSN: 0378-4274
Factor impacto JCR: 3.858 (2016)
Categ. JCR: TOXICOLOGY rank: 14 / 92 = 0.152 (2016) - Q1 - T1
Factor impacto SCIMAGO: 1.302 - Toxicology (Q1) - Medicine (miscellaneous) (Q1)
Financiación: info:eu-repo/grantAgreement/EC/FP7/604387/EU/Assessment and mitigation of nano-enabled product risks on human and environmental health: Development of new strategies and creation of a digital guidance tool for nanotech industries/GUIDENANO
Tipo y forma: Congress (Published version)
Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you may not distribute the modified material.
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Ceria nanoparticles (CeO2 NPs) have several industrial applications and pharmacological potential due to their antioxidant properties. However, toxicity data on CeO2 NPs are scarce and show contradictory results. In the present study, uncoated, polyethylene glycol- and citrate-coated CeO2 NPs (4-8 nm) were administrated to C57Bl/6 mice by repeated dose (3×) pharyngeal aspiration using four different doses of each type of NPs (corresponding to 4.4, 8.8, 17.6 and 35.2 µg Ce2+/mouse/aspiration), and sampled 1 and 28 days after the last administration. DNA damage was assessed by the comet assay locally in bronchoalveolar lavage (BAL) and lung cells, and systemically in liver cells. Micronuclei, a biomarker of chromosome damage, were analysed in bone marrow and peripheral blood erythrocytes. Immunotoxicity was evaluated by BAL cell counting. Furthermore, histopathological effects on the lungs and biodistribution of the NPs (analysis of Ce2+ in several organs) were assessed. At 24-h, a significant increase in DNA damage was induced at the highest doses by uncoated and citrate-coated NPs in BAL cells. For these NPs a significant, but non-dose-dependent, effect was observed in lung and liver cells at 28-d. No systemic genotoxic effects were observed with any of the NPs. A dose-dependent accumulation of macrophages and activated lymphocytes was seen in the lungs for all the NPs, although a milder reaction was elicited by the coated NPs. Our findings show that short-term exposure of mice to CeO2 NPs induces pulmonary inflammation, and non-dose-dependent DNA damage, but no systemic genotoxicity. (Funded by the EU FP-7 GUIDEnano, Grant Agreement No.604387).
Idioma: Inglés
DOI: 10.1016/j.toxlet.2016.06.1965
Año: 2016
Publicado en: TOXICOLOGY LETTERS 258, Suppl. (2016), S276 [P17-045]
ISSN: 0378-4274
Factor impacto JCR: 3.858 (2016)
Categ. JCR: TOXICOLOGY rank: 14 / 92 = 0.152 (2016) - Q1 - T1
Factor impacto SCIMAGO: 1.302 - Toxicology (Q1) - Medicine (miscellaneous) (Q1)
Financiación: info:eu-repo/grantAgreement/EC/FP7/604387/EU/Assessment and mitigation of nano-enabled product risks on human and environmental health: Development of new strategies and creation of a digital guidance tool for nanotech industries/GUIDENANO
Tipo y forma: Congress (Published version)
Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you may not distribute the modified material. Exportado de SIDERAL (2020-02-21-13:49:23)
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Record created 2018-11-07, last modified 2020-02-21