Measurement of ?-glucuronidase in effluent of perifused alveolar macrophages challenged with chemically modified chrysotile asbestos

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Abstract
Chrysotile asbestos has been implicated with lung disorders, notably fibrotic lesions and cancer. In vitro, chrysotile fibers are cytotoxic to lung macrophages and stimulate the release of inflammatory mediators. Reports to the effect that chemical modifications of asbestos fibers reduce their cytotoxic and inflammatory potential initiated the present study of three fiber modifications. The cytotoxic and inflammatory effects of magnesium-leached chrysotile, POCL3-treated chrysotile, and CaO-treated chrysotile were studied in a perifused rat alveolar macrophage culture system, relative to untreated fibers. Natural Canadian chrysotile (UICC “B”) caused dose-dependent cell mortality and clumping. The release ofβ-glucuronidase (β-Glu), a lysosomal enzyme, was also dose dependent. Rhodesian chrysotile (UICC “A”) caused similar cytotoxic and inflammatory effects. However, magnesium-leached chrysotile was less cytotoxic (39% less) and had a lesser clumping capacity (31% less) than untreated chrysotile. Total secretion ofβ-Glu elicited by magnesium-leached chrysotile was reduced by 43% from the untreated sample, but kinetic monitoring indicates that this reduction in inflammatory potential is only significant during the first 12 h of an 18-h culture period. POCl3 treatment of chrysotile fibers produced differing effects depending on the length of the fibers under study. Treating fibers with a mean length of 8 μm produced a secretion pattern similar to that produced by acid leaching. The total output for the treated sample was 44% lower than with untreated chrysotile; the difference was only significant during the first 12 h of perifusion. Cell mortality and aggregation were not reduced in any important way with POCl3 treatment of these longer fibers. When ultra-short fibers (mean length=0.8 μm) were treated with POCl3, the total decrease inβ-Glu output was equal to 41%, and the release of enzyme was significantly lower during the whole 18-h experiment. Cell aggregation was not appreciably affected, but cell mortality was significantly lower than for untreated fibers. CaO treatment did not alter the cytotoxic (cell death and aggregation) or inflammatory (β-Glu release) effects of chrysotile asbestos. These results suggest that chemical modifications affecting the integrity of the surface magnesium and/or the polarity of the surface charge of chrysotile can reduce to some extent the cytotoxic and inflammatory properties of this type of asbestos.