DIRECT INTERACTION BETWEEN CRYSTALLINE SILICA AND DNA - A PROPOSED MODEL FOR SILICA CARCINOGENESIS

Crystalline silica in aqueous buffer produced oxygen radicals that med iated in vitro DNA (deoxyribonucleic acid) strand breakage. The oxidiz ed DNA base, thymine glycol, was also produced. The hydroxyl radical, responsible for most DNA damage, has a reaction distance of about 15 A ngstroms, requiring close contact of silica with DNA. Fourier transfor m infrared spectroscopy of incubations of quartz particles with DNA sh owed distinct alterations in both DNA and quartz spectra and therefore indicated extensive hydrogen bonding between surface silanol groups a nd the phosphate-sugar backbone of DNA. Electron microscopy and energy dispersive X-ray spectroscopy of alveolar epithelial cells in fetal r at lung, exposed to quartz in culture, showed localization of quartz p articles in the nuclei and mitotic spindles. Direct interaction of cry stalline silica with DNA may be important in silica carcinogenesis by anchoring DNA close to sites of free radical production on the silica surface, or by interfering with DNA replication, repair, or the mitoti c process.