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Cell-electronic Sensing of Cellular Responses and Toxicity Induced by Nanoparticles and Arsenic Species

  • Author / Creator
    Moe, Birget K
  • We demonstrate the development of a real-time cell analysis (RTCA) platform for studying nanoparticle- and arsenic-induced cytotoxicity with potential applications to risk assessment, environmental toxicity monitoring, and drug development. RTCA is an impedance-based in vitro detection system capable of simultaneously performing 96 cytotoxicity tests. To develop a RTCA method for nanoparticle-mediated cytotoxicity testing, we examined two well-characterized nanoparticles, titanium dioxide and silver nanoparticles, and used three cell lines, A549, SK-MES-1, and CHO-K1. Continuous real-time sensing provided qualitative and quantitative data, revealing concentration-, particle-, time-, and cell-dependent toxicological relationships. We further applied our RTCA method to evaluate cytotoxicity of air particulate matter (PM), including coal fly ash (CFA) and PM2.5 collected on air monitoring filters, using two human lung cell lines, A549 and SK-MES-1. The RTCA method was able to overcome the interference commonly encountered in colorimetric toxicity assays, making the RTCA approach potentially useful in air quality monitoring. Real-time cell sensing also enabled toxicity ranking of thirteen arsenic species in two human cancer cell lines, A549 and T24, and revealed unique kinetic information about cellular responses to the various arsenic species. Testing of a newly synthesized arsenical, Arsenicin A, showed that it was more toxic than the inorganic arsenic species. Analysis of cell accumulation of arsenic species suggests that a higher intracellular accumulation of Arsenicin A compared to inorganic arsenic is a major contributor to its higher toxicity. Determination of the chemical conversion of arsenic species in cell culture media over time provided insights into understanding the unique RTCA profiles of cells responding to some arsenic species. Co-treatment of a human cancer cell line, A549, with arsenic species and oxidized single-walled carbon nanotubes (SWCNT) showed that the SWCNT altered the toxicity of the arsenic species to the cancer cells. SWCNT reduced the cytotoxicity of a highly toxic trivalent phenylarsenical, but enhanced the cytotoxicity of a less toxic pentavalent phenylarsenical. The changes in arsenic toxicity were dependent on the dose of SWCNT in combination with the dose of arsenic species. These results suggest a potential application of RTCA to research on drug development.

  • Subjects / Keywords
  • Graduation date
    2013-11
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3H38K
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Medical Sciences- Laboratory Medicine and Pathology
  • Supervisor / co-supervisor and their department(s)
    • Li, Xing-Fang (Laboratory Medicine and Pathology)
  • Examining committee members and their departments
    • Leslie, Elaine (Physiology)
    • Hugh, Judith (Laboratory Medicine and Pathology)
    • Krylov, Sergey (Chemistry, York University)
    • Le, X. Chris (Laboratory Medicine and Pathology)
    • Acker, Jason (Laboratory Medicine and Pathology)