Genotoxicity evaluation of three classes of manufactured nanomaterials on primary human lymphocytes

Conference object English OPEN
Tavares, Ana ; Louro, Henriqueta ; Antunes, Susana ; Quarré, Stéphanie ; Simar, Sophie ; Nesslany, Fabrice ; Silva, Maria João (2012)
  • Publisher: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
  • Subject: Genotoxicidade Ambiental | Nanomateriais

Human exposure to manufactured nanomaterials (MNMs) through consumers’ goods has increased worldwide, including titanium dioxide (TiO2), multiwalled carbon-nanotubes (MWCNT) and silicon dioxides (SiO2). Specific properties of MNMs, such as size and high surface area/mass, render them attractive for many applications, but may also be associated to higher toxicity in biological systems and adverse effects in humans. In the context of an EU Joint Action (NANOGENOTOX), aimed at establishing a robust methodology for evaluation of the MNMs genotoxicity, the objective of the present work was to characterize the potential genotoxic effects of a panel of well-characterized MNMs in human lymphocytes. Cultures of lymphocytes from healthy volunteers were exposed to several non-cytotoxic concentrations of four TiO2, six MWCNT and four SiO2 MNMs, dispersed according to a previously established procedure, for 30h; concurrent positive controls included a chemical (mitomycin C) and a reference nanosized ZnO. The cytokinesis-block micronucleus assay was performed according to the OECD guideline 487 and the frequencies of micronucleated binucleate (MNBNC) and mononucleate cells were determined. The results showed that slight but significant increases in the frequencies of MNBNC were observed for some TiO2 NMs and MWCNTs, as compared to controls, while all SiO2 NMs were negative in the micronucleus assay; a single dose of ZnO was able to significantly induce MNBNC. However, no clear monotonic dose-response relationships could be disclosed, not enabling clear conclusions about the genotoxicity of the tested MNMs. No influence on cell cycle progression and cell viability was noted by the cytokinesis-block proliferation index. In summary, although the micronucleus assay in primary human lymphocytes is suitable to evaluate the genotoxicity of MNMs following standardized dispersion and assay procedures, data from other cell lines or from other endpoints (e.g. comet assay) have to be gathered in order to achieve a robust genotoxicity evaluation.
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