| RRC ID |
62915
|
| 著者 |
Ahmed S, Kobayashi H, Afroz T, Ma N, Oikawa S, Kawanishi S, Murata M, Hiraku Y.
|
| タイトル |
Nitrative DNA damage in lung epithelial cells exposed to indium nanoparticles and indium ions.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Indium compounds have been widely used in manufacturing displays of mobile phones, computers and televisions. However, inhalation exposure to indium compounds causes interstitial pneumonia in exposed workers and lung cancer in experimental animals. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed under inflammatory conditions and may participate in indium-induced carcinogenesis. In this study, we examined 8-nitroG formation in A549 cultured human lung epithelial cells treated with indium compounds, including nanoparticles of indium oxide (In2O3) and indium-tin oxide (ITO), and indium chloride (InCl3). We performed fluorescent immunocytochemistry to examine 8-nitroG formation in indium-exposed A549 cells. All indium compounds significantly increased 8-nitroG formation in A549 cells at 5 ng/ml after 4 h incubation. 8-NitroG formation was largely reduced by 1400 W, methyl-β-cyclodextrin (MBCD) and monodansylcadaverine (MDC), suggesting the involvement of nitric oxide synthase and endocytosis. 8-NitroG formation in A549 cells was also largely suppressed by small interfering RNA (siRNA) for high-mobility group box-1 (HMGB1), receptor for advanced glycation and end products (AGER, RAGE) and Toll-like receptor 9 (TLR9). These results suggest that indium compounds induce inflammation-mediated DNA damage in lung epithelial cells via the HMGB1-RAGE-TLR9 pathway. This mechanism may contribute to indium-induced genotoxicity in the respiratory system.
|
| 巻・号 |
10(1)
|
| ページ |
10741
|
| 公開日 |
2020-7-1
|
| DOI |
10.1038/s41598-020-67488-3
|
| PII |
10.1038/s41598-020-67488-3
|
| PMID |
32612147
|
| PMC |
PMC7329867
|
| MeSH |
A549 Cells
Antigens, Neoplasm / genetics
Antigens, Neoplasm / metabolism
DNA Damage*
Guanine / analogs & derivatives*
Guanine / metabolism
HMGB1 Protein / genetics
HMGB1 Protein / metabolism
Humans
Indium / administration & dosage
Indium / chemistry
Indium / pharmacology*
Lung Neoplasms / genetics
Lung Neoplasms / metabolism
Lung Neoplasms / pathology*
Mitogen-Activated Protein Kinases / genetics
Mitogen-Activated Protein Kinases / metabolism
Mutagens
Nanoparticles / administration & dosage*
Nanoparticles / chemistry
Toll-Like Receptor 9 / genetics
Toll-Like Receptor 9 / metabolism
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
A549(RCB0098) |
