Genotoxicity evaluation of nanosized titanium dioxide, synthetic amorphous silica and multi-walled carbon nanotubes in human lymphocytes

Tavares, Ana; Louro, Henriqueta; Antunes, Susana; Quarré, Stephanie; Simar, Sophie; Temmerman, Pieter-Jan De; Verleysen, Eveline; Mast, Jan; Jensen, Keld Alstrup; Norppa, Hannu; Nesslany, Fabrice; Silva, Maria João

doi:10.1016/j.tiv.2013.06.009

Cited by 105 publications

(68 citation statements)

References 50 publications

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“…In this study we also failed to see any significant increase of micronuclei after treatment with TiO 2 NPs in spite of a significant production of ROS and of 8-oxodG. Induction of micronuclei or chromosome aberrations were reported in several studies even though the observed effects were often mild and not clearly dose related, reflecting a rather weak clastogenic properties of TiO 2 NPs greatly influenced by the experimental model and conditions (Catalán et al, 2012;Falck et al, 2009;Kang et al, 2008;Prasad et al, 2013;Tavares et al, 2014).…”

Section: Discussioncontrasting

confidence: 53%

Different mechanisms are involved in oxidative DNA damage and genotoxicity induction by ZnO and TiO2 nanoparticles in human colon carcinoma cells

Zijno

Angelis

Berardis

et al. 2015

Toxicology in Vitro

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Section: Discussioncontrasting

confidence: 53%

Different mechanisms are involved in oxidative DNA damage and genotoxicity induction by ZnO and TiO2 nanoparticles in human colon carcinoma cells

Zijno

Angelis

Berardis

et al. 2015

Toxicology in Vitro

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“…However, a weak genotoxic effect was detected by the micronucleus assay in colon cells from rats treated by gavage with the two pyrogenic silica nanoparticles (NM-202 and NM-203) [12]. On the other hand, the four silica nanoparticles that we used were unable to induce in vitro micronuclei in human lymphocytes [8], and micronucleus assays were negative in Balb/c 3T3 exposed to NM-200 or NM-203 [14].…”

Section: Discussionmentioning

confidence: 75%

“…Data on the genotoxic properties of SAS, mostly assessed by the comet assay for detecting DNA damage or by the micronucleus assay for chromosomal damage, are however less clear. Generally, positive responses in genotoxicity assays are reported more frequently in vitro [5][6][7][8][9] than in vivo [10][11][12]. However, in vitro results remain quite variable and depend on the physical and chemical characteristics of the SAS and the cell type used.…”

Section: Introductionmentioning

confidence: 99%

In vitro cell transformation induced by synthetic amorphous silica nanoparticles

Fontana

Kirsch

Seidel

et al. 2017

Mutation Research/Genetic Toxicology and Environmental Mutagene

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International audienceSynthetic amorphous silica nanoparticles (SAS) are among the most widely produced and used nanomaterials, but little is known about their carcinogenic potential. This study aims to evaluate the ability of four different SAS, two precipitated, NM-200 and NM-201, and two pyrogenic, NM-202 and NM-203, to induce the transformation process. For this, we used the recently developed in vitro Bhas 42 cell transformation assay (CTA). The genome of the transgenic Bhas 42 cells contains several copies of the v-Ha-ras gene, making them particularly sensitive to tumor-promoter agents. The Bhas 42 CTA, which includes an initiation assay and a promotion assay, was validated in our laboratory using known soluble carcinogenic substances. Its suitability for particle-type substances was verified by using quartz Min-U-Sil 5 (Min-U-Sil) and diatomaceous earth (DE) microparticles. As expected given their known transforming properties, Min-U-Sil responded positively in the Bhas 42 CTA and DE responded negatively. Transformation assays were performed with SAS at concentrations ranging from 2 µg/cm 2 to 80 µg/cm 2. Results showed that all SAS have the capacity to induce transformed foci, interestingly only in the promotion assay, suggesting a mode of action similar to tumor-promoter substances. NM-203 exhibited transforming activity at a lower concentration than the other SAS. In conclusion, this study showed for the first time the transforming potential of different SAS, which act as tumor-promoter substances in the Bhas 42 model of cell transformation.Les nanoparticules de silice amorphes de synthèse (SAS) sont les nanomatériaux les plus produits et les plus utilisés dans le monde, mais leur potentiel cancérogène est peu étudié. Cette étude avait pour but d’évaluer la capacité de quatre différentes SAS, deux sous forme précipitée, NM-200 et NM-201 et deux sous forme pyrogénée, NM-202 et NM-203, d’induire des processus de cancérogénèse. Pour cela, nous avons utilisé l’essai de transformation sur les cellules Bhas 42 (Bhas 42 CTA) qui a été récemment développé. Le génome des cellules Bhas 42 transgéniques contient plusieurs copies du gène v-Ha-ras, ce qui leur confère les caractéristiques de cellules « initiées » et les rend particulièrement sensibles aux agents promoteurs de tumeur. Le Bhas 42 CTA, qui inclut un essai d’initiation et un essai de promotion, a été validé dans notre laboratoire en utilisant des agents cancérogènes solubles connus. Son adaptabilité pour des substances de type particule a été vérifié en utilisant des microparticules de quartz Min-U-Sil 5 (Min-U-Sil) et de terre de diatomée (DE). Comme attendu d’après leur propriété transformante connue, le Min-U-Sil a répondu positivement et la DE négativement au Bhas 42 CTA. Les essais de transformation ont été réalisés à des concentrations de SAS s’étalant de 2 µg/cm2 à 80 µg/cm2. Les résultats montrent que toutes les SAS ont la capacité d’induire des foyers de transformation et de manière intéressante, uniquement dans l’essai de promotion, suggérant...

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“…In addition, 13 out of 18 studies report increased micronuclei frequency in human cell lines after exposure to MWCNTs, including three independent studies of MWCNT-7 (Muller et al 2008a, 2008b; Asakura et al 2010; Cveticanin et al 2010; Migliore et al 2010; Di Giorgio et al 2011; Srivastava et al 2011; Kato et al 2013; Wu et al 2013; Darne et al 2014; Tavares et al 2014; Visalli et al 2015; Kim et al 2016); five studies showed null effects (Szendi & Varga 2008; Thurnherr et al 2011; Lindberg et al 2013; Ponti et al 2013; Mrakovcic et al 2015). Eight out of 13 studies report increased micronuclei frequency in human cell lines after exposure to either SWCNTs or MWCNTs (Cveticanin et al 2010; Migliore et al 2010; Cicchetti et al 2011; Di Giorgio et al 2011; Kisin et al 2011; Manshian et al 2013; Darne et al 2014; Kim & Yu 2014; Kim et al 2016); five studies showed null effects (Kisin et al 2007; Lindberg et al 2009; Lindberg et al 2013; Pelka et al 2013; Mrakovcic et al 2015).…”

Section: Genotoxicitymentioning

confidence: 99%

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

Kuempel

Jaurand

Møller

et al. 2016

Critical Reviews in Toxicology

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In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials. The findings of this review, in general, affirm those of the original evaluation on the inadequate or limited evidence of carcinogenicity for most types of CNTs and CNFs at this time, and possible carcinogenicity of one type of CNT (MWCNT-7). The key evidence gaps to be filled by research include: investigation of possible associations between in vitro and early-stage in vivo events that may be predictive of lung cancer or mesothelioma, and systematic analysis of dose–response relationships across materials, including evaluation of the influence of physico-chemical properties and experimental factors on the observation of nonmalignant and malignant endpoints.

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Genotoxicity evaluation of nanosized titanium dioxide, synthetic amorphous silica and multi-walled carbon nanotubes in human lymphocytes

Cited by 105 publications

References 50 publications

Different mechanisms are involved in oxidative DNA damage and genotoxicity induction by ZnO and TiO2 nanoparticles in human colon carcinoma cells

Different mechanisms are involved in oxidative DNA damage and genotoxicity induction by ZnO and TiO2 nanoparticles in human colon carcinoma cells

In vitro cell transformation induced by synthetic amorphous silica nanoparticles

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

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