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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 (In<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>) and indium-tin oxide (ITO), and indium chloride (InCl<jats:sub>3<\/jats:sub>). 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\u00a0ng\/ml after 4\u00a0h incubation. 8-NitroG formation was largely reduced by 1400\u00a0W, methyl-\u03b2-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 (<jats:italic>HMGB1<\/jats:italic>), receptor for advanced glycation and end products (<jats:italic>AGER<\/jats:italic>, RAGE) and Toll-like receptor 9 (<jats:italic>TLR9<\/jats:italic>). 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.<\/jats:p>","DOI":"10.1038\/s41598-020-67488-3","type":"journal-article","created":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T10:40:20Z","timestamp":1593600020000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Nitrative DNA damage in lung epithelial cells exposed to indium nanoparticles and indium ions"],"prefix":"10.1038","volume":"10","author":[{"given":"Sharif","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatasu","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahmina","family":"Afroz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Oikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shosuke","family":"Kawanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Hiraku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,1]]},"reference":[{"key":"67488_CR1","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.ceramint.2007.02.015","volume":"34","author":"E Medvedovski","year":"2008","unstructured":"Medvedovski, E., Alvarez, N., Yankov, O. & Olsson, M. 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