Genotoxicity and Gene Expression in the Rat Lung Tissue following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NM).

Fátima Brandão,Florence Debacq-Chainiaux,Anne Bannuscher,Carla Costa,Bryan Hellack,Michel Salmon,Sami Gharbia,João Paulo Teixeira,Sónia Fraga,Elise Dumortier,Roland Hubaux,Maria João Bessa,Miruna S Stan,Anca Hermenean,Julie Laloy,Andrea Haase,Anca Dinischiotu

doi:10.3390/nano11061502

Abstract

Several reports on amorphous silica nanomaterial (aSiO2 NM) toxicity have been questioning their safety. Herein, we investigated the in vivo pulmonary toxicity of four variants of aSiO2 NM: SiO2_15_Unmod, SiO2_15_Amino, SiO2_7 and SiO2_40. We focused on alterations in lung DNA and protein integrity, and gene expression following single intratracheal instillation in rats. Additionally, a short-term inhalation study (STIS) was carried out for SiO2_7, using TiO2_NM105 as a benchmark NM. In the instillation study, a significant but slight increase in oxidative DNA damage in rats exposed to the highest instilled dose (0.36 mg/rat) of SiO2_15_Amino was observed in the recovery (R) group. Exposure to SiO2_7 or SiO2_40 markedly increased oxidative DNA lesions in rat lung cells of the exposure (E) group at every tested dose. This damage seems to be repaired, since no changes compared to controls were observed in the R groups. In STIS, a significant increase in DNA strand breaks of the lung cells exposed to 0.5 mg/m3 of SiO2_7 or 50 mg/m3 of TiO2_NM105 was observed in both groups. The detected gene expression changes suggest that oxidative stress and/or inflammation pathways are likely implicated in the induction of (oxidative) DNA damage. Overall, all tested aSiO2 NM were not associated with marked in vivo toxicity following instillation or STIS. The genotoxicity findings for SiO2_7 from instillation and STIS are concordant; however, changes in STIS animals were more permanent/difficult to revert.

Highlights

Silica (SiO2 ) nanomaterials (NM) are currently produced in large-scale and are amongst the most widely commercialized manufactured NM
Primary and oxidative DNA damage were evaluated in total lung cell suspensions by the standard and Formamidopyrimidine DNA glycosylase (FPG)-modified alkaline comet assay versions, respectively
We have investigated effects on DNA integrity, protein carbonylation and gene expression in the lung tissue of rats exposed to different variants of aSiO2 NM, either by instillation or short-term inhalation study (STIS)

Summary

Introduction

Silica (SiO2 ) nanomaterials (NM) are currently produced in large-scale and are amongst the most widely commercialized manufactured NM. Amorphous silica nanomaterials (aSiO2 NM) are being extensively used for industrial purposes as biosensors and catalytic supports, stabilizers of emulsions or foams for enhanced oil recovery processes, for the improvement of the mechanical characteristics of polymers and composites, or as additives for paints/lacquers/coatings [1,3]. This wide range of industrial applications and growing commercial production obviously increased the likelihood of human exposure to aSiO2 NM, mainly through inhalation [4,5]. Reports on genetic damage induced for most NM are consistent with indirect genotoxic effects rather than direct interaction of NM with

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