Journal
TOXICOLOGY MECHANISMS AND METHODS
Volume 17, Issue 4, Pages 223-232Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/15376510600943775
Keywords
cell killing; chromosome damage; crystalline silica; DNA damage; human; cells; mutation; ultrafine particles
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Respirable quartz is a potential human lung carcinogen. The mechanisms involved in this carcinogenesis, however, remain unclear, especially for the ultrafine particles (diameter <100 nm). The aim of the present study was to investigate the effects caused by ultrafine quartz (UF-quartz) in a human cell culture model. Genotoxicity and cytotoxicity induced by UF-quartz were investigated through the cytokinesis block micronucleus assay (CBMN), the Comet assay, the HPRT assay, the population growth assay, and the 3-(4, 5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. WIL2-NS cells were incubated for 10h with 0, 60, and 120 mu g/mL UF-quartz. Significant decreases in percent of cell survival in the MTT assay were seen at higher doses, for example, 83%, and 64% relative survival at 60 mu g/mL and 120 mu g/mL, respectively. Only slight population regrowth was observed, with the population sizes recovering slightly by day 4 after quartz particles were removed. A significant increase in the frequency of micronucleated binucleated cells (MNed BNCs) was seen with 120 mu g/mL quartz, from approximately 5 in 1000 BNCs in controls to 12 in 1000 BNCs. A significant reduction in the nuclear division index was observed by the CBMN assay, indicating inhibition of cell division by high-dose UF-quartz. A dose-dependent increase in induced HPRT-gene locus mutant frequency with increasing dose of UF-quartz was observed by the HPRT assay. No significant difference was found in DNA strand breakage as detected by the Comet assay. Collective findings suggest that UF-quartz can cause cytotoxicity and genotoxicity to human lymphoblasts in this model system.
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