Journal Article

Silica-Induced Generation of Extracellular Factor(s) Increases Reactive Oxygen Species in Human Bronchial Epithelial Cells

Alina Deshpande, Padma K. Narayanan and Bruce E. Lehnert

in Toxicological Sciences

Volume 67, issue 2, pages 275-283
Published in print June 2002 | ISSN: 1096-6080
Published online June 2002 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/67.2.275
Silica-Induced Generation of Extracellular Factor(s) Increases Reactive Oxygen Species in Human Bronchial Epithelial Cells

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Chronic inflammation and production of DNA-damaging reactive oxygen species (ROS) may be involved in silica-induced lung cancer. Studies to date have largely focused on silica-induced production of ROS by lung phagocytes. In this study, we investigated the hypothesis that particulate silica (DQ12) can also induce elevations in intracellular ROS in a cancer-target cell type, i.e., human bronchial epithelial cells (BECs), via an indirect mechanism that involves ROS-inducing extracellular factor(s) that occur upon the interaction of silica with culture medium. The intracellular production of hydrogen peroxide (H2O2) in BECs was assessed by flow cytometry via monitoring dichlorofluorescein (DCF) fluorescence. Culture medium containing 10% human serum was incubated with silica particles in concentrations ranging from 10 to 50 μg/ml, and following incubation for 1 h and removal of the particles, the resulting supernatants were added to BECs. Silica-treated medium induced significant increases in intracellular H2O2 after the medium had been treated with as little as 10 μg/ml of the particles. Further, the level of ROS increases in BECs in response to silica-treated medium was found to be virtually identical to that induced in cells that were directly treated with silica in suspension. Based on enzyme inhibitory studies, the mechanism for this increased generation of intracellular ROS appears to involve both mitochondrial respiration and a NAD(P)H oxidase-like system. Spectrofluorimetric experiments with the antioxidant enzymes superoxide dismutase and catalase showed that superoxide anions (O2•−) and H2O2 are generated in silica-treated medium, but these ROS do not fully account for the induction of the intracellular ROS response. Iron, on the other hand, was found to be crucial to the process. Our collective results suggest silica-aqueous medium interactions can lead to the generation of factor(s) that induce the intracellular production of potentially DNA-damaging ROS in BECs in a manner that does not require direct particle-cell interactions.

Keywords: human bronchial epithelial cells; silica; reactive oxygen species; free radicals; extracellular factors

Journal Article.  6980 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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