DNA STRAND BREAKAGE, THYMINE GLYCOL PRODUCTION, AND HYDROXYL RADICAL GENERATION INDUCED BY DIFFERENT SAMPLES OF CRYSTALLINE SILICA IN-VITRO

Five preparations of alpha-quartz [Min-U-Sil 5 (MQZ), MQZ pretreated w ith hydrofluoric acid (HFMQZ), Chinese standard alpha-quartz (CSQZ), a nd two German samples, DQ-12 and F600] and two preparations of the cry stalline silica polymorphs, cristobalite and tridymite, previously cha racterized for surface area and surface charge, were evaluated for the ir relative activities in the following assays: (i) in vitro assays of short duration (less than or equal to 15 min) for oxygen consumption and for generation of hydroxyl radicals (measured by electron spin res onance spin trapping), and (ii) in vitro assays of longer duration for DNA strand breakage (measured using linear DNA as a detector molecule ) and for production of the oxidized DNA base, thymine glycol (measure d by gas chromatography-mass spectrometry). Marked differences among t he samples were found for their levels of oxygen consumption and of hy droxyl radicals' generation. All samples caused increased formation of thymine glycol, with wide variations in activity among samples. When normalized for equal surface area, the samples produced different leve ls of DNA strand breakage. Addition of hydrogen peroxide strongly acce lerated DNA damage-more for cristobalite than for the alpha-quartz sam ples. DNA damage by quartz was enhanced by ferric chloride and inhibit ed by iron chelators. The order of relative activity of the samples va ried with different types of in vitro assays and was not directly corr elated to surface area. Electrophoretic mobility, as measured by zeta potential, was not significantly different among samples. The results suggest that the ability of different crystalline silica samples to ge nerate a rapid burst of oxygen free radicals is distinct from their ab ility to induce DNA damage and DNA base oxidation over longer time per iods. The relative activities of the samples in cellular assays (hemol ysis of human erythrocytes; cytotoxicity and neoplastic transformation of BALB/3T3/A31 . 1 . 1 cells) were in turn markedly different from t hose listed above, suggesting a more critical role for surface area. T he mechanisms of carcinogenesis by crystalline silica need to be furth er investigated in relation 60 the underlying physicochemical characte ristics. (C) 1995 Academic Press, Inc.