Nitrative DNA damage in cultured macrophages exposed to indium oxide

Access this Article

Author(s)

Abstract

<p><b>Objectives: </b>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. <b>Methods: </b>We treated RAW 264.7 mouse macrophages with indium oxide (In<sub>2</sub>O<sub>3</sub>) 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 In<sub>2</sub>O<sub>3</sub>-treated cells by the Griess method. We also examined the effects of inhibitors of inducible NO synthase (iNOS) and endocytosis on In<sub>2</sub>O<sub>3</sub>-induced 8-nitroG formation. <b>Results: </b>In<sub>2</sub>O<sub>3</sub> significantly increased the intensity of 8-nitroG formation in RAW 264.7 cells in a dose-dependent manner. In<sub>2</sub>O<sub>3</sub>-induced 8-nitroG formation was observed at 2 h and further increased at 4 h, and the amount of NO released from In<sub>2</sub>O<sub>3</sub>-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). <b>Conclusions: </b>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.</p>

Journal

  • Journal of Occupational Health

    Journal of Occupational Health 60(2), 148-155, 2018

    Japan Society for Occupational Health

Codes

  • NII Article ID (NAID)
    130006565471
  • NII NACSIS-CAT ID (NCID)
    AA11090645
  • Text Lang
    ENG
  • ISSN
    1341-9145
  • NDL Article ID
    028896377
  • NDL Call No.
    Z54-J76
  • Data Source
    NDL  J-STAGE 
Page Top