Year: 2008
Type: dissertation
Abstract: The colony formation assay (CFA) is the gold standard for measuring cytotoxic effects on cells. To increase efficiency, the CFA was converted to a 96-well format using an automated colony counting algorithm. The 96-well CFA was validated using ionizing radiation (IR) on the FaDu and A549 cancer cell lines. Its ability to evaluate combination therapies was investigated using cisplatin and IR. The 96-well CFA was transferred to a robotic platform for evaluation as a high-throughput screen (HTS) readout for the discovery of novel anti-cancer compounds, and radiosensitizers. Screening yielded eight putative anti-cancer hits, and five putative radiosensitizing hits. Secondary screening confirmed 6/8 anti-cancer compounds, and 0/5 radiosensitizing compounds. Thus, the 96-well CFA can be adopted as an alternative assay to the 6-well CFA in the evaluation of cytotoxicity in vitro, providing a possible readout to be utilized in HTS for discovering anti-cancer compounds, but with limited applicability in discovering radiosensitizers. ii Acknowledgements First and foremost, I would like to extend great thanks to my supervisor, Dr. Fei-Fei Liu, for her incredible guidance and support during my two years as a Master Student. Her mentorship has guided me through both my research and in establishing my career path. She will continue to be a role model to me throughout my career. As well, I would like to thank the members of my supervisory committee, Dr. Aaron Schimmer and Dr. Suzanne Trudel. They have kept me on track and provided integral advice with respect to the best path for my research to follow. I would also like to thank the members
Source: TSpace (University of Toronto)
Author: David R. Katz
Language: English
Subfield: Radiation
Field: Physics and Astronomy
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W2102287009