Abstract
The Ministry of Health, Labor and Welfare, Japan, recently, reported that several cases of acute silicosis occurred among workers who handling high-purity crystalline silica. Silicosis is known to associate with an increased risk of lung cancer, and the IARC classifies crystalline silica as a Group 1 carcinogen.
Genotoxic events are known to be fundamental in the initiation of cancer. Based on in vivo studies, it has been proposed that generation of oxidative DNA damage due to silica-induced inflammation may play an important role for development of lung cancer. On the other hand, although various in vitro genotoxicity tests have been conducted on whether crystalline silica can generate DNA damage independently of inflammation, the results remain controversial. In this study, we aimed to examine whether crystalline silica induces DNA damage independently of inflammatory response.
A549 (human lung adenocarcinoma epithelial cell line) and CHL/IU (Chinese hamster lung cell line) cells were treated with respirable crystalline silica MIN-U-SIL (primary median particle size: 1.6 μm) and generation of DNA damage were assessed by γ-H2AX assay. We observed clear dose-dependent (from 25 μg/cm2) formation of γ-H2AX at 24 h after exposure to MIN-U-SIL in both cell lines without apoptotic cell death. During mechanistic investigation, we found that heat treatment of Min-U-Sil clearly suppressed γ-H2AX generation. Furthermore, we confirmed that the amount of silanol group in MIN-U-SIL was reduced by heat treatment. These results suggested that the silanol group in surface of MIN-U-SIL are crucial to generate γ-H2AX. In this study, we concluded that respirable crystalline silica can form DNA damage independently of inflammatory reaction, and the surface condition of particles would be important for genotoxic effect.
