Evidence supporting a role for active oxygen species in asbestos-induced toxicity and lung disease.

Abstract

Asbestos is an important occupational and environmental toxicant that affects several cell types in the respiratory tract. In an effort to understand how asbestos causes cell injury and/or altered proliferation and differentiation of cells, this laboratory has focused on reactive oxygen species as mediators of asbestos-induced biological effects. A compendium of experimental results reported by this laboratory and others supports this hypothesis. For example, scavengers of reactive oxygen metabolites and iron chelators (i.e., desferroxamine) prevent cytotoxicity after addition of asbestos to a variety of cell lines and macrophages in vitro. DNA strand breakage associated with toxicity of crocidolite asbestos in C3H10T 1/2 cells also is ameliorated with use of desferroxamine. All types of asbestos cause lipid peroxidation in mammalian cells and artificial membranes, a phenomenon that can be prevented by removal of catalytic iron. Last, asbestos causes generation of active oxygen species after interaction with leukocytes or by reduction of oxygen on the surface of the fibers.ImagesFIGURE 1.

Mineral fibre toxicity: expression of retinoblastoma (Rb) and phospho-retinoblastoma (pRb) protein in alveolar epithelial and mesothelial cell lines exposed to fluoro-edenite fibres

“…It has been proposed that the cytotoxic and genotoxic effects of asbestos fibres may also be related to their content in ferrous/ferric ions, which induces iron-mediated generation of reactive oxygen species and/or reactive nitrogen species (Hansen and Mossman 1987;Korkina et al 1992;Mossman and Marsh 1989). The iron found in these fibres is thought to be an important factor in the generation of • OH from reduction of O 2 or decomposition of H 2 O 2 .…”

Immunohistochemical localization of transforming growth factor-β and insulin-like growth factor-I in asbestosis in the sheep model

“…This initial inflammatory response consists of an accumulation of alveolar macrophages in the alveolar ducts and peribronchiolar regions of the terminal respiratory bronchiole, followed by an influx of interstitial macrophages and fibroblasts, which results in interstitial thickening [12,15,46]. Migrating asbestos fibers and oxidants released by activated macrophages also injure adjacent cells, including type I alveolar epithelial cells [15,31,39,41], which results in compromise of epithelial integrity and allows access of growth factors and cytokines to the interstitium. As part of the healing process, type II epithelial cell hyperplasia develops and is accompanied by interstitial fibrosis with deposition of extracellular matrix proteins.…”

Induction of Manganese Superoxide Dismutase Gene Expression in Bronchoepithelial Cells after Rockwool Exposure

“…In the context of dust-induced inflammatory processes in the lung, reactive oxygen species are already important factors in the initial lung response to mineral particulate exposure [2,30,34,49]. Exposure to fibers may induce an imbalance of the oxidantantioxidant system on the epithelial surface of the airways.…”

“…Exposure to fibers may induce an imbalance of the oxidantantioxidant system on the epithelial surface of the airways. Depending on the fiber size, the surface area of these fibers, the iron content of the fiber surface, the surface charge, and the incubation time, this imbalance is considered to contribute significantly to the severity of the disease [22,30,34,38,46]. To maintain the oxidant-antioxidant balance, bronchoepithelial cells contain an antioxidative defense system consisting predominantly of superoxide dismutases (SODs), glutathione, and catalase [28].…”