title: Enhanced generation of free radicals from phagocytes induced by mineral dusts.
abstract: Several studies have suggested that pulmonary toxicity to asbestos and silica may be mediated through oxidant-induced cell injury. We have reported recently that surface radicals associated with freshly fractured silica may be an important factor in cell injury and induction of pulmonary disease. Although the generation of oxygenated radicals in dust-cell interactions has been demonstrated, there are no data correlating the toxicity of a dust with the level of oxygen radical generation by the dust during its interaction with phagocytic cells. In the present study, we have investigated the in vitro generation of oxygen free radicals from human neutrophils and rat alveolar macrophages stimulated with freshly fractured silica, aged silica, amosite, crocidolite, chrysotile, and nontoxic dust, barite. Electron spin resonance (ESR) with the aid of a spin trap phenyl-N-tert-butyl nitrone (PBN) was used to measure the oxygen radicals generated during phagocytosis of the dusts. The relative toxicity index and ESR peak heights, on an equal surface area basis and normalized to barite as one, showed a direct relationship. The normalized toxicity indices and peak heights were: silica, 3.5 versus 2; chrysotile, 4 versus 2; crocidolite, 11 versus 8; and amosite, 26 versus 13. Addition of hydroxyl radical scavengers such as catalase, dimethyl sulfoxide, 1,3 dimethyl-2-thiourea (DMTU), sodium benzoate, and mannitol prevented the radical generation. Carmustine, a glutathione reductase-glutathione peroxidase inhibitor, caused a 5-fold increase in the radical generation. These results indicate that a nontoxic dust such as barite generates toxic oxygen radicals at a minimal level that can be quenched by the normal cellular defense system. For toxic dusts such as silica, amosite, chrysotile, and crocidolite, the potential for oxygen radical generation is enhanced by their surface properties, physical dimensions, and the surface-based radical-generating redox sites. The enhanced radical generation may impair the cellular defense system, resulting in cell injury. Use of scavengers, chelators, and potentiating agents suggests the membrane-based oxidase system as the probable primary source of the radical-generating system. The data presented herein suggest the generation of oxygen free radicals as an important primary event in silica- as well as asbestos-induced cell injury.
authors.affiliation: Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV 26505.
authors.forename: V
authors.initials: V
authors.lastname: Vallyathan
authors.forename: J F
authors.initials: JF
authors.lastname: Mega
authors.forename: X
authors.initials: X
authors.lastname: Shi
authors.forename: N S
authors.initials: NS
authors.lastname: Dalal
mesh_terms: D000818:Animals; D001194:Asbestos / Q000494:pharmacology*; D017639:Asbestos, Amosite; D017638:Asbestos, Crocidolite; D017632:Asbestos, Serpentine; D001466:Barium Sulfate / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D004391:Dust; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D005609:Free Radicals; D006801:Humans; D007501:Iron / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012822:Silicon Dioxide / Q000494:pharmacology
chemical_list: D017632:Asbestos, Serpentine; D004391:Dust; D016166:Free Radical Scavengers; D005609:Free Radicals; D017638:Asbestos, Crocidolite; D017639:Asbestos, Amosite; D001194:Asbestos; D001466:Barium Sulfate; D012822:Silicon Dioxide; D007501:Iron