Evidence of a no-effect level in silica-induced rat lung mutagenicity but not in fibrogenicity

Exposure to silica can lead to fibrosis and the development of lung tumors in the rat. Based on these animal studies and on epidemiological data, sili ca has been classified as a human carcinogen. The initial mechanisms have n ot been finally clarified, but particle-induced tumor formation is at least closely associated with inflammation, the production of reactive oxygen sp ecies (ROS) and DNA damage. We investigated the dose-dependent effects of s ilica on the formation of the major DNA oxidation product 8-oxoguanine (8-o xoGua) in rat lung cells, on p53 (p53) and p53 mutant protein (p53 mut) syn thesis, as well as on the amount of the surfactant phospholipids phosphatid ylinositol (PI) and phosphatidylglycerol (PG) in the bronchoalveolar lavage fluids (BALF) as indicators of fibrotic processes in the lung. Rats were e xposed by intratracheal instillation to various amounts of DQ12 quartz (0.1 5, 0.3, 0.6, 1.2, 2.4 mg/animal) and lungs were investigated after 21 and 9 0 days. PG decreased and PI increased quartz dose dependently. 8-oxoGua was significantly increased only after 1.2 and 2.4 mg quartz/animal. Cells exp ressing p53 protein were increased at 1.2 and 2.4 mg, p53 mutant protein on ly at 2.4 mg/animal. This indicates a no-effect level for mutagenicity at a low, but still fibrogenic quartz exposure.