論文 - 詳細
| RRC ID | 67320 |
|---|---|
| 著者 | Afroz T, Hiraku Y, Ma N, Ahmed S, Oikawa S, Kawanishi S, Murata M. |
| タイトル | Nitrative DNA damage in cultured macrophages exposed to indium oxide. |
| ジャーナル | J Occup Health |
| Abstract |
OBJECTIVES:Indium compounds are used in manufacturing displays of mobile phones and televisions. However, these materials cause interstitial pneumonia in exposed workers. Animal experiments demonstrated that indium compounds caused lung cancer. Chronic inflammation is considered to play a role in lung carcinogenesis and fibrosis induced by particulate matters. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed during inflammation and may participate in carcinogenesis. To clarify the mechanism of carcinogenesis, we examined 8-nitroG formation in indium-exposed cultured cells. METHODS:We treated RAW 264.7 mouse macrophages with indium oxide (In2O3) nanoparticles (primary diameter: 30-50 nm), and performed fluorescent immunocytochemistry to detect 8-nitroG. The extent of 8-nitroG formation was evaluated by quantitative image analysis. We measured the amount of nitric oxide (NO) in the culture supernatant of In2O3-treated cells by the Griess method. We also examined the effects of inhibitors of inducible NO synthase (iNOS) and endocytosis on In2O3-induced 8-nitroG formation. RESULTS:In2O3 significantly increased the intensity of 8-nitroG formation in RAW 264.7 cells in a dose-dependent manner. In2O3-induced 8-nitroG formation was observed at 2 h and further increased at 4 h, and the amount of NO released from In2O3-exposed cells was significantly increased at 2-4 h compared with the control. 8-NitroG formation was suppressed by 1400W (an iNOS inhibitor), methyl-β-cyclodextrin and monodansylcadaverine (inhibitors of caveolae- and clathrin-mediated endocytosis, respectively). CONCLUSIONS:These results suggest that endocytosis and NO generation participate in indium-induced 8-nitroG formation. NO released from indium-exposed inflammatory cells may induce DNA damage in adjacent lung epithelial cells and contribute to carcinogenesis. |
| 巻・号 | 60(2) |
| ページ | 148-155 |
| 公開日 | 2018-3-27 |
| DOI | 10.1539/joh.17-0146-OA |
| PMID | 29187674 |
| PMC | PMC5886882 |
| MeSH | Amidines / pharmacology Animals Benzylamines / pharmacology Cadaverine / analogs & derivatives Cadaverine / pharmacology Cells, Cultured DNA Damage / drug effects* Dose-Response Relationship, Drug Guanine / analogs & derivatives* Guanine / biosynthesis Immunohistochemistry Indium / pharmacology* Macrophages / drug effects* Mice Nanoparticles Nitric Oxide / biosynthesis Nitric Oxide Synthase Type II / antagonists & inhibitors Particle Size beta-Cyclodextrins / pharmacology |
| IF | 2.289 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |