Generation of free radicals from phagocytic cells by mineral dusts was studied in-vitro. Neutrophils isolated from the blood of healthy human donors and alveolar macrophages from male Sprague- Dawley-rats were incubated with 250 micrograms per milliliter (microg/ml) barite (7727437) or freshly fractured or aged silica (14808607) or 50microg/ml amosite (12172735), chrysotile (12001295), or crocidolite (12001284). Production of oxygen radicals was assessed by electron spin resonance (ESR) spectroscopic analysis. Similar experiments were conducted with the radical scavengers catalase, superoxide-dismutase, glutathione, dimethyl-sulfoxide (DMSO), 1,3-dimethyl-2-thiourea (DMTU), sodium-benzoate, or mannitol or the radical potentiating agents carmustine, NADPH, or allopurinol present in the incubation mixtures. All of the dusts except barite induced significant formation of oxygen radicals in the cells. The mean ESR peak heights of the radical signals of the various dusts were: aged silica 1.12 millimeters (mm), amosite 1.41mm, chrysotile 1.45mm, crocidolite 2.07mm, and freshly fractured silica 2.08mm. The mean peak height of barite was 0.81mm, which did not differ significantly from the control value 0.65mm. Catalase, DMSO, DMTU, glutathione, sodium-benzoate, and mannitol inhibited formation of oxygen radicals by the dusts. These effects suggested that hydrogen- peroxide played an important role in radical generation and that the hydroxyl radical may be the predominant radical species generated. Carmustine and NADPH significantly enhanced radical production. When these data were combined with previously obtained cytotoxicity data and normalized to barite, the normalized toxicity and ESR peak height indices were: silica 3.5 versus 2, chrysotile 4 versus 2, crocidolite 11 versus 8, and amosite 26 versus 13. The authors conclude that generation of oxygen free radicals plays an important role in silica and asbestos (1332214) dust induced cell injury, and that the potential for free radical generation is enhanced by the surface properties, physical dimensions, and active surface sites of these dusts. Nontoxic dusts such as barite induce a low level of oxygen radicals, but they are controlled by normal cell detoxication systems.
Val Vallyathan, Ph.D., NIOSH Pathology Section, 944 Chestnut Ridge Road, MS 204, Morgantown, WV 26505