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Is there a link between the physicochemical characteristics of multiwalled carbon nanotubes and their genotoxicity in human cells?

Publication . Louro, Henriqueta; Pinhão, Mariana; Tavares, Ana; Vital, Nádia; Borges, Teresa; Gouveia, Helena; Silva, Maria João

The wide applicability of manufactured nanomaterials (NM) has led to an increased risk of human exposure and environmental dissemination. In particular, multi-walled carbon nanotubes (MWCNT) have been developed for industrial purposes, but the same properties that render these materials so attractive may also cause higher toxicity. However, contradictory results concerning their genotoxicity and carcinogenicity have been reported, suggesting that minor changes in physicochemical properties may determine their toxicity. The objective of this work was to characterize the cyto- and genotoxic effects of MWCNTs that differ in thickness, length and aspect ratio (NM-401, NM-402 and NM-403, JRC repository) in human-derived bronchial epithelial cells (BEAS-2B), in order to ascertain which characteristic(s) may be determinant for their genotoxicity. After NM dispersion using a standardized protocol, cell cultures were exposed to several NM concentrations (0-256 μg/ml). Cell viability was evaluated by the Trypan blue dye exclusion assay. For genotoxicty testing, a combination of the alkaline comet assay (3- or 24h- exposure) and the cytokinesis-blocked micronucleus assay (48h-exposure) was used. The results showed that NM-401 and NM-403 were cytotoxic following 24h exposure, whereas the highest doses of NM-402 were cytotoxic at 3h. The genotoxicity results in relation to the different MWCNT tested were not consistent, indicating that diameter and length are rather important properties that influence the genotoxic potential of these NM. In summary, our work confirmed that the standard genotoxicity tests can be applied for evaluating the genotoxicity of different types of MWCNT. However, we also concluded that specific physicochemical properties impact on the genotoxic potential of these high aspect ratio NM, an issue that has to be further understood, possibly by targeted testing. Regarding safety assessment and related regulatory aspects, the differential genotoxicity observed for closely related NM highlights the importance of investigating the toxic potential of each NM individually, instead of assuming a common mechanism and equal genotoxic effects for a set of similar NM.

2014-10-23Conference object

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Genotoxicity of synthetic amorphous silica nanoparticles in rats following short-term exposure. Part 1: Oral route

Publication . Tarantini, Adeline; Huet, Sylvie; Jarry, Gérard; Martine, Poul; Tavares, Ana; Vital, Nádia; Louro, Henriqueta; Silva, Maria João; Fessard, Valérie

Synthetic amorphous silica (SAS) in its nanosized form is now used in food applications although the potential risks for human health have not been evaluated. In this study, genotoxicity and oxidative DNA damage of two pyrogenic (NM-202 and 203) and two precipitated (NM-200 and -201) nanosized SAS were investigated in vivo in rats following oral exposure. Male Sprague Dawley rats were exposed to 5, 10, or 20 mg/kg b.w./day for three days by gavage. DNA strand breaks and oxidative DNA damage were investigated in seven tissues (blood, bone marrow from femur, liver,spleen, kidney, duodenum, and colon) with the alkaline and the (Fpg)-modified comet assays, respectively. Concomitantly, chromosomal damage was investigated in bone marrow and in colon with the micronucleus assay. Additionally, malondialdehyde (MDA), a lipid peroxidation marker, was measured in plasma. When required, a histopathological examination was also conducted. The results showed neither obvious DNA strand breaks nor oxidative damage with the comet assay, irrespective of the dose and the organ investigated. Similarly, no increases in chromosome damage in bone marrow or lipid peroxidation in plasma were detected. However, although the response was not dose-dependent, a weak increase in the percentage of micronucleated cells was observed in the colon of rats treated with the two pyrogenic SAS at the lowest dose (5 mg/kg b.w./day). Additional data are required to confirm this result, considering in particular, the role of agglomeration/aggregation of SAS NMs in their uptake by intestinal cells.

2015-03Journal article

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Avaliação integrada dos efeitos genotóxicos de nanomateriais manufaturados no ratinho transgénico LacZ

Publication . Louro, Henriqueta; Tavares, Ana; Vital, Nádia; Costa, Pedro M.; Alverca, Elsa; Lavinha, João; Silva, Maria João

Num estudo recente, demonstrámos que um nanomaterial de dióxido de titânio na forma cristalina designada anatase, o NM-102 (do repositório do Joint Research Center; Ispra, Itália), induziu um aumento significativo de quebras cromossómicas - detetáveis na forma de micronúcleos - em linfócitos humanos expostos ex vivo(3) não se tendo, porém, observado um efeito dose-resposta. No sentido de prosseguir e aprofundar a avaliação da genotoxicidade do NM-102, o presente estudo teve por objetivo caracterizar os seus efeitos genotóxicos, num modelo animal, utilizando uma abordagem integrada, a qual abrangeu a análise de vários parâmetros de genotoxicidade no mesmo animal.

2014Journal article

Open access

Role of nanogenotoxicology studies in safety evaluation of nanomaterials

Publication . Louro, Henriqueta; Bettencourt, Ana; Gonçalves, Lídia M.; Almeida, António J.; Silva, Maria João

Nanomaterials (NMs) are defined as materials containing particles where one or more external dimensions are in the size range of 1 100 nm. Many different NMs, alone or in combination,in the form of fibers, tubes, or particles have been already proposed for innovative diagnostic, drug delivery platforms and nanostructured matrices for tissue engineering applications. Presently, the diversity of NMs that are being used, or explored as candidates, for tissue engineering can be classified into different groups (polymers, ceramics,carbon nanotubes [CNTs], metals and composites), depending on their chemical composition. This chapter describes the importance of genotoxicity evaluation to warrant the safety of these innovative NMs, with particular emphasis on the most prominent testing strategies that must consider and incorporate the specific physicochemical characteristics of the nanosized materials into toxicological research.

2015-01Book part

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