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 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.

Modification of pulmonary silicotic reaction in rats exposed to coal fly ash.

Quartz exposure resulted in an increase in the wet weight, dry weight and collagen contents of lungs. Animals inoculated comparable amounts of fly ash revealed a statistically insignificant increase in these parameters. In silicotic rats exposed to fly ash the increase in the wet weight, dry weight and collagen contents of lungs was reduced in comparison to silicotic animals unexposed to coal fly ash. Histological examination of lungs revealed the development of silicotic granulomata with reticulin and collagen fibre formation. The difference in the development of these lesions was less pronounced when a blindfold comparison was made between the silicotic animals, exposed or unexposed to coal fly ash. The increased activity of LDH in the bronchoalveolar lavage (BAL) of rats exposed to quartz alone was mitigated significantly in silicotic animals subsequently exposed to coal fly ash. The protein content of the BAL increased significantly more in quartz-fly ash exposed animals than in rats exposed to either dust alone. The total cellular elements of the BAL were increased in rats exposed to quartz alone (p less than 0.005). The results demonstrate that fly ash exposure can significantly modify the development of a silicotic pulmonary reaction.