DNA STRAND BREAKS FOLLOWING IN-VITRO EXPOSURE TO ASBESTOS INCREASE WITH SURFACE-COMPLEXED [FE3+]

Surface functional groups on silicate dusts complex iron cations which can cycle through reduction and oxidation states to generate free rad icals. These oxidants have a capacity to produce DNA strand breaks and mutations which are primary events in cancer induction. A differentia l in the capacity of fibrous silicates to produce carcinoma is recogni zed with the amphiboles demonstrating a greater biologic effect than t he serpentine fiber chrysotile. We tested the hypothesis that the diff erences in genotoxicity of these fibrous silicates correspond to varyi ng concentrations of iron complexed to the surface. Relative to chryso tile, the amphibole fibers complexed greater amounts of iron cations f rom both inorganic and in vivo sources. Increased concentrations of su rface-complexed iron were associated with greater oxidant generation, measured as thiobarbituric acid-reactive products of deoxyribose, and more covalently closed, circular DNA strand scission. These results in dicate that genotoxic effects of these fibers may correspond to their capacity to complex iron at the surface. (C) 1994 Academic Press, Inc.