Variability of biological responses to silicas: effect of origin, crystallinity, and state of surface on generation of reactive oxygen species and morphological transformation of mammalian cells.

Variously modified quartz dusts and one amorphous diatomaceous earth have been compared in their potential to release HO* radicals and in their activity in the Syrian hamster embryo (SHE) cell transformation assay. Both original dusts, made up by well-crystallized quartz particles, or by mostly amorphous, variously shaped, silica particles, were active in HO* release, were cytotoxic, and induced morphological transformation in SHE cells. The cristobalite dust, obtained by heating quartz above the phase transition temperature, lost any activity in free radical release, cytotoxicity, and transforming potency. Surface-modified quartz dusts were obtained by a mild etching with HF, by depriving the surface of trace iron with deferoxamine, or by enriching it with iron. The chemical and biological activity decreased in all cases. Both iron-deprived and iron-enriched quartz were nearly inactive. A linear correlation was found between the amount of HO* released by the particles and the transformation frequency. When the SHE cell assay was performed in the presence of mannitol or antioxidant enzymes (superoxide dismutase [SOD] or catalase), the number of transformed cells markedly decreased. This effect was more pronounced for catalase and mannitol than for SOD. HO* release was reduced, but not suppressed, by deferoxamine. All the above results are consistent with the presence of two kinds of surface sites active in HO* release and cell transformation: (1) silicon-based radicals, abundant on freshly ground dusts, which generate the HO* radicals without the superoxide ion as intermediate; and (2) isolated iron centers where the Haber-Weiss cycle takes place, with the superoxide ion as intermediate. The activities of both sites are inhibited by mannitol or catalase, whereas only the last one is inhibited by SOD.