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

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 μg/ml ultrafine crystalline SiO2 (UF‐SiO2). The cytotoxic and genotoxic effects caused by UF‐SiO2 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‐SiO2 in the methyl tetrazolium assay. Significant decreases were seen at 120 μg/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‐SiO2 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 μg/ml UF‐SiO2 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 μg/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 μg/ml as detected by the hypoxanthine guanine phosphoribosyltransferase mutation assay. The results indicate that UF‐SiO2 is cytotoxic and genotoxic in cultured human cells. Environ. Mol. Mutagen., 2007. © 2007 Wiley‐Liss, Inc.