Direct interaction between crystalline silica and DNA - a proposed model for silica carcinogenesis.
Crystalline silica in aqueous buffer produced oxygen radicals that mediated in vitro DNA (deoxyribonucleic acid) strand breakage. The oxidized DNA base, thymine glycol, was also produced. The hydroxyl radical, responsible for most DNA damage, has a reaction distance of about 15 Angstroms, requiring close contact of silica with DNA. Fourier transform infrared spectroscopy of incubations of quartz particles with DNA showed distinct alterations in both DNA and quartz spectra and therefore indicated extensive hydrogen bonding between surface silanol groups and the phosphate-sugar backbone of DNA. Electron microscopy and energy dispersive X-ray spectroscopy of alveolar epithelial cells in fetal rat lung, exposed to quartz in culture, showed localization of quartz particles in the nuclei and mitotic spindles. Direct interaction of crystalline 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 mitotic process.
Daniel
L N
LN
Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892-0041, USA.
Mao
Y
Y
Williams
A O
AO
Saffiotti
U
U
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003460:Crystallization; D004247:DNA / Q000378:metabolism*; D008854:Microscopy, Electron; D051381:Rats; D012822:Silicon Dioxide / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared
D002273:Carcinogens; D012822:Silicon Dioxide; D004247:DNA