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 C3H1OT½ 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.

Mechanisms of Multistep Carcinogenesis and Carcinogen Risk Assessment

“…Whether this is strictly a promotional effect of asbestos remains to be elucidated. Finally, there is a number ofobservations indicating that asbestos induces cellular and biochemical changes, such as hyperplasia, metaplasia, DNA synthesis, and stimulation ofoxygen free-radicals that are typical of known tumor promoters (61,62). By analogy to other promoters, therefore, it has been suggested that asbestos is operating through promotional mechanisms.…”

Asbestos-exposed blood monocytes - deoxyribonucleic acid strand lesions in co-cultured bronchial epithelial cells

“…Similarly stimulated phagocytes are able to produce cytogenetic changes in mammalian cells (17). The concept of a mechanism inducing the iron-catalyzed generation of reactive oxygen intermediates after the direct contact of several cell types with asbestos resulting in genotoxicity and cytotoxicity has been supported by the results of various studies (28,29). The inflammatory and mutagenic potential of the asbestos-dependent release of reactive oxygen intermediates is due to the iron-mediated Fenton-reaction, which generates highly reactive hydroxyl radicals.…”

Mineral fiber-mediated activation of phosphoinositide-specific phospholipase c in human bronchoalveolar carcinoma-derived alveolar epithelial A549 cells

“…These variations may lead to the production of different levels and perhaps various species of radicals by individual asbestos types (17)(18)(19). Since asbestos fibers contain ferrous/ferric ions, it has proposed that the cytotoxic and genotoxic effects of asbestos fibers may be related to the generation of reactive oxygen species and/or reactive nitrogen species mediated by iron (20)(21)(22). Iron present in asbestos fibers is thought to be an important factor in the generation of…”