Oxidative DNA damage induced by silica in vivo.

Occupational exposure to silica has often been associated with the development of pulmonary fibrosis and, occasionally, lung cancer. Their development may be mediated by oxidant-induced cellular injury. The short- and long-term effects of a single intratracheal instillation of silica in rats (10 mg/200 microliters/saline per rat) was assessed by measuring 8-hydroxy-2'-deoxyguanosine (oh8dG) levels in lung tissue and peripheral blood leukocytes. Cell differentials, reduced glutathione (GSH), and superoxide dismutase (SOD), lipid peroxide, and total phospholipids in peripheral blood and/or bronchoalveolar lavage fluid (BALF) were also measured. The pulmonary oh8dG levels increased approximately 2.24- 2.86-fold from 1 to 5 days after exposure to silica. It was still elevated 1 and 4 weeks after installation, but the difference was no longer statistically significant. The oh8dG levels in peripheral blood leukocytes were never significantly different, but they were generally higher than in the controls. The low SOD levels in the BALF of exposed rats in the early stage and the higher GSH levels in the late stage may represent protective reactions against the generation of oxygen species. A significant increase in oh8dG levels in lung tissue suggested the possible carcinogenicity of silica.