Cytotoxicity and genotoxicity of ultrafine crystalline SiO₂ particulate in cultured human lymphoblastoid cells

Abstract

Respirable crystalline silica has been classified as a human lung carcinogen. Ultrafine (diameter < 100 nm) silica particles may be important in carcinogenesis, although the mechanisms remain unclear. In the present study, WIL2-NS cells were incubated for 6, 24, and 48 hr with 0, 30, 60, and 120 microg/ml ultrafine crystalline SiO(2) (UF-SiO(2)). The cytotoxic and genotoxic effects caused by UF-SiO(2) in cultured human cells were investigated via a set of bioassays. Significant dose- dependent decreases in percent cell viability were seen with increasing dose of UF-SiO(2) in the methyl tetrazolium assay. Significant decreases were seen at 120 microg/ml (58, 38, and 57% for 6, 24, and 48-hr exposure, respectively). During 4 days growth in the flasks, there was a slight recovery observed after washing off UF-SiO(2) as measured by the population growth assay. Significant dose-dependent reduction in the cytokinesis block proliferation index was observed by the cytokinesis block micronucleus assay. Treatment with 120 microg/ml UF-SiO(2) for 24 hr produced a fourfold increase in the frequency of micronucleated binucleated cells (MNBNC). The increase in MNBNC was dose-dependent. The lowest dose that gave a statistically significant increase in MNBNC was 30 microg/ml (24-hr treatment), which had cytotoxicity of less than 10%. There was no significant difference in DNA strand breakage as measured by the Comet assay. A significant increase in induced mutant frequency was found at 120 microg/ml as detected by the hypoxanthine guanine phosphoribosyltransferase mutation assay. The results indicate that UF-SiO(2) is cytotoxic and genotoxic in cultured human cells.

Evaluation of cytotoxic concentration–time response in A549 cells exposed to respirable α‐quartz

“…In general the reactivity of the particle surface is closely related to the ability of quartz to generate ROS (Fubini et al, 1990), and since ROS are implicated in both DNA damage and carcinogenesis (Marnett, 2000), it was postulated that the particle surface is involved in DNA damage induced by quartz. Cytotoxic and genotoxic eff ects of crystalline silica were evidenced in some in vitro studies (Elias et al, 2000;Lin et al, 2006;Wang et al, 2007;Fanizza et al, 2007). Moreover silicainduced cytokine release from human epithelial lung cell line (Hetland et al, 2001) and from human alveolar macrophages (Gosset et al, 1991) was found.…”

Cytotoxicity and DNA damage in mouse macrophages exposed to silica nanoparticles

“…SiO 2 nanoparticles caused dose-dependent cell toxicity in cultivated human broncho-alveolar carcinoma-derived cells (A549) and increased oxidative stress (Lin et al, 2006), release of various cytokines from RAW 264.7 macrophages (Park et al, 2011a), decreased fibroblast viability at high doses (Chang et al, 2007), and lung fibrosis in Wistar rats (Chen et al, 2004). Cellular and genetic toxicity of ultrafine crystalline SiO 2 (diameter <100 nm) particles were found to in cultivated human cells (Wang et al, 2007). In addition, a study in mice indicated that SiO 2 nanoparticles are non-poisonous and can therefore be applied to in vivo (Xue et al, 2006).…”

Genotoxic effects of three selected black toner powders and their dimethyl sulfoxide extracts in cultured human epithelial A549 lung cells in vitro

“…The effects of these samples were compared to those of Dörentrup quartz DQ12, which has a genotoxic potential and may contribute to the carcinogenicity of silica in humans. Respirable quartz powder has been classified as a Group 1 carcinogen [IARC, 1997] and has been investigated in numerous studies [Donaldson and Borm, 1998;Fubini, 1998;Rimal et al, 2005;Wang et al, 2007]. Furthermore, benzo[a]pyrene (B[a]P), a PAH known to be a human carcinogen, was chosen as a second positive control in the genotoxicity assays.…”