title: Surface modification of quartz inhibits toxicity, particle uptake, and oxidative DNA damage in human lung epithelial cells.
abstract: 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.
authors.affiliation: Institut für Umweltmedizinische Forschung an der Heinrich-Heine-Universität, Düsseldorf, D-40225, Germany. roel.schins@uni-duesseldorf.de
authors.forename: Roel P F
authors.initials: RP
authors.lastname: Schins
authors.forename: Rodger
authors.initials: R
authors.lastname: Duffin
authors.forename: Doris
authors.initials: D
authors.lastname: Höhr
authors.forename: Ad M
authors.initials: AM
authors.lastname: Knaapen
authors.forename: Tingming
authors.initials: T
authors.lastname: Shi
authors.forename: Christel
authors.initials: C
authors.lastname: Weishaupt
authors.forename: Vicki
authors.initials: V
authors.lastname: Stone
authors.forename: Ken
authors.initials: K
authors.lastname: Donaldson
authors.forename: Paul J A
authors.initials: PJ
authors.lastname: Borm
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004578:Electron Spin Resonance Spectroscopy; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000032:analysis; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010316:Particle Size; D011791:Quartz / Q000009:adverse effects* / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D013499:Surface Properties
chemical_list: D011791:Quartz; D017665:Hydroxyl Radical; D007770:L-Lactate Dehydrogenase; D003849:Deoxyguanosine