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.

Nanotoxicology and nanoparticle safety in biomedical designs

“…These differences are mainly due to particle surface characteristics. 15 The specific cytotoxicity of silica is strongly correlated with the appearance of surface radicals and reactive oxygen species (ROS), which is considered a key event in the development of fibrosis and lung cancer caused by this compound. 16 Although the type of particle does not seem to play an important role in whether it is embedded in the surfactant lining of the alveoli, the embedding process itself is crucial.…”

Pathological study of pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): Effects of lowered serum zinc level on the toxicity

“…Quartz (crystalline silica) is known to generate cytotoxic and genotoxic effects in pneumocytes [30]. Amorphous and crystalline silica (SiO 2 ) [31][32][33][34][35][36], as well as ASD [9,10,[37][38][39][40] have been reported to cause inflammatory responses and damage with the release of inflammatory cytokines including IL-6 and TNF and with the generation of reactive oxygen species (ROS) in the lungs of experimental animals.…”

Nanomaterials for biomedical applications

“…Paclitaxel encapsulated in vitamin E TPGS-emulsified poly(D, L-Lactic-c-glycolic acid) (PLGA) NPs showed enhanced cytotoxicity for tumor cells in vitro, and it maintained a sustainable therapeutic potential in an animal model system (Win & Feng 2006). Poly-4-vinylpyridine N-oxide (PVNO) polymer coated micro quartz particles were shown to have efficient distribution without showing any macrophage related toxicity and genotoxicity (Schins et al 2002;Albrecht et al 2005). Polyethylene glycol (PEG) coated magnetic NPs of 40-50 nm size are reported to be well taken up by endocytosis (Gupta & Curtis 2004).…”