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Induction of Neoplastic Transformation, AP‐1 Signaling, PDCD4 signaling, and DNA Damage by Copper Oxide Nanoparticles Involves ROS‐Mediated MAPK Pathways in JB6 Cells.
Author(s) -
Barber Tabatha L.,
Aldinger Joni,
Tenney Allyson,
Leonard Stephen,
Morris Anna,
Ding Min
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb644
Subject(s) - reactive oxygen species , mapk/erk pathway , dna damage , signal transduction , microbiology and biotechnology , chemistry , neoplastic transformation , biochemistry , carcinogenesis , biology , dna , gene
Occupational exposures to copper dusts or fumes have beenreported to be harmful to human health, with possible risk of cancer amongcopper smelting workers. Copper (II)oxide (CuO) nanoparticles have not, to our knowledge, been extensively examinedfor potential carcinogenic or genotoxic effects. To investigate the mechanismsof CuO‐induced pathogenesis, the effect of CuO on AP‐1‐MAPKs and ROS generation were investigated. The results indicated that CuO caused a 2‐fold increase in AP‐1 activity in JB6 cells. The induction of AP‐1 activity in cultured cell lines was time and dose‐dependent. The signal transduction pathways for AP‐1 activation were also investigated. Western Blotanalysis demonstrate that CuO nanoparticles stimulate phosphorylation of p38MAPK and ERKs. CuO also generated ROS when incubated with the cells as measured by electron spin resonance (ESR). Nano‐sized CuO generated more ROS than the fine sized particles when incubated with the cells. COMET assay suggests that exposure of the cells to CuO resulted in DNA damage. Cells pre‐treated with ROS inhibitors sodium formate and Polyvinylpyridine‐N‐Oxide (PVPNO) before exposure to CuO nanoparticles demonstrate a significant reduction in p‐38 and ERK activity, suggesting the H 2 O 2 may have a role in the ROS mechanism. Soft agar transformation assays demonstrated that there is a significant increase in colony formation in JB6/AP‐1 cells treated with CuO nanoparticles as compared to the control, indicative of neoplastictransformation. Unraveling the complex mechanisms associated with these events may provide insights into the initiation and progression of CuO‐induced pathogenesis. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .