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Aneugenic and Clastogenic Effects of Amorphous Silica Nanoparticles in A549 Human Lung Carcinoma Cells: Size Matters?

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Background/Aims: This study aimed at re-assessing the genotoxic potential of amorphous nanoparticles (SNPs) with emphasis on size-effects, applying the criteria recommended by us (Gonzalez et al. 2008).
Methods: The in vitro cytochalasin-B micronucleus assay (CBMN assay) was applied to SNPs with three different diameters (16, 60 and 104 nm) in A549 human lung carcinoma cells. The cellular dose was determined by inductively -coupled plasma mass spectroscopy. Mechanisms of SNP-induced genotoxicity were investigated by the alkaline comet assay (with and without FPG) and FISH with pancentromeric probes, that was used to make a distinction between the formation of micronuclei containing either chromosome fragments or entire chromosomes after treatment with 40 and 60 µg/ml of 16 and 60 nm SNPs. Mitotic indices and induction of mitotic slippage were investigated in parallel with the CBMN assay.
Results and conclusions: The in vitro CBMN assay showed an induction of MN frequencies after treatment with the 16 and 104 nm SNPs, with a higher fold induction after treatment with the smallest SNPs. The cellular dose, expressed as particle number or as surface area, is an adequate dose metric for determinants of MN induction. Besides oxidative damage (alkaline comet assay + fpg), 16 and 60 nm SNPs induce other genotoxic effects, such as chromosome loss, metaphase block and mitotic slippage, suggesting interference with the mitotic spindle.
Tijdschrift: Environmental & Molecular Mutagenesis
ISSN: 0893-6692
Issue: 7
Volume: 50
Pagina's: 555-555
Jaar van publicatie:2009
Trefwoorden:nanoparticles, aneugenicity, clastogenicity