Surface Modification of Quartz Inhibits Toxicity, Particle Uptake, and Oxidative DNA Damage in Human Lung Epithelial Cells

Quartz (crystalline silica) is not consistently carcinogenic across different industries where similar quartz exposure occurs. In addition, there are reports that surface modification of quartz affects its cytotoxicity, inflammogenicity, and fibrogenicity. Taken together, these data suggest that the...

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Bibliographic Details
Published in:Chemical research in toxicology 2002-09, Vol.15 (9), p.1166-1173
Main Authors: Schins, Roel P. F, Duffin, Rodger, Höhr, Doris, Knaapen, Ad M, Shi, Tingming, Weishaupt, Christel, Stone, Vicki, Donaldson, Ken, Borm, Paul J. A
Format: Article
Language:English
Subjects:
Cell Survival
Cells, Cultured
Comet Assay
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - analysis
DNA Damage
Electron Spin Resonance Spectroscopy
epithelial cells
Epithelial Cells - cytology
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Humans
Hydroxyl Radical - analysis
Immunohistochemistry
L-Lactate Dehydrogenase - analysis
Lung - cytology
Lung - drug effects
Lung - metabolism
Oxidation-Reduction
Particle Size
Quartz - adverse effects
Quartz - antagonists & inhibitors
Quartz - pharmacokinetics
Surface Properties
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Summary:Quartz (crystalline silica) is not consistently carcinogenic across different industries where similar quartz exposure occurs. In addition, there are reports that surface modification of quartz affects its cytotoxicity, inflammogenicity, and fibrogenicity. Taken together, these data suggest that the carcinogenicity of quartz is also related to particle surface characteristics, and so we determined the genotoxic effects of DQ12 quartz particles versus DQ12 whose surface was modified by treating with either aluminum lactate or polyvinylpyridine-N-oxide (PVNO). The different particle preparations were characterized for hydroxyl-radical generation using electron spin resonance (ESR). DNA damage was determined by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) and the alkaline comet-assay using A549 human lung epithelial cells. Cytotoxicity was measured using the LDH- and MTT-assays, and particle uptake by the A549 cells was quantified by light microscopy, using digital light imaging evaluation of 800 nm sections. The ability of quartz to generate hydroxyl-radicals in the presence of hydrogen peroxide was markedly reduced upon surface modification with aluminum lactate or PVNO. DNA strand breakage and 8-OHdG formation, as produced by quartz at nontoxic concentrations, could be completely prevented by both coating materials. Particle uptake into A549 cells appeared to be significantly inhibited by the PVNO-coating, and to a lesser extent by the aluminum-lactate coating. Our data demonstrate that respirable quartz particles induce oxidative DNA damage in human lung epithelial cells and indicates that surface properties of the quartz as well as particle uptake by these target cells are important in the cytotoxic and the genotoxic effects of quartz in vitro.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx025558u