title: 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.
authors.affiliation: Department of Public Health, University of Adelaide, South Australia 5005, Australia. wang0311@flinders.edu.au
authors.forename: Jing J
authors.initials: JJ
authors.lastname: Wang
authors.forename: Barbara J S
authors.initials: BJ
authors.lastname: Sanderson
authors.forename: He
authors.initials: H
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D052638:Particulate Matter; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*; D012828:Silicones; D014407:Tumor Cells, Cultured
chemical_list: D009153:Mutagens; D052638:Particulate Matter; D012828:Silicones; D012822:Silicon Dioxide; D007041:Hypoxanthine Phosphoribosyltransferase