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- W2100054331 abstract "Purpose/Objective(s): Tumor Treating Fields (TTFields), currently used as an antimitotic modality, induce forces on polar macromolecules resulting in impaired mitotic spindle function. TTFields are expected to affect negatively charged, small DNA fragments produced by ionizing radiation (IR). Such an effect can result in impaired ligation of DNA strand breaks causing IR sensitization and decreased tumor survival. The objective of the present work is to test TTFields effect on DNA Damage Repair. Materials/Methods: A model describing the effects of TTFields on small DNA fragments was constructed and evaluated by measuring DNA migration in gel electrophoresis during TTFields application. Experimentally, TTFields effects on DNA strand breaks repair alone and in combination with IR were studied in glioma and non-small cell lung cancer (NSCLC) cells using the comet assay, g-H2AX foci formation, and RAD51 foci formation and resolution. Cell survival was measured by MTT and cell count as well as clonogenic survival. Results: Within the framework of the theoretical model, DNA fragments of about 400 bp oscillate over a distance of one base-pair at TTFields frequency of 100 kHz, while larger fragments are not affected. Support for the model was provided by the analysis of fragment mobility in gel electrophoresis. The comet assay demonstrated that TTFields reduce repair of IR-induced DNA damage in glioma cells. Treatment with a combination of IR and TTFields resulted in increased number of g-H2AX and RAD51 foci compared with either treatment alone. Importantly, in both glioma and NSCLC cells combination of IR and TTFields reduced cell viability and clonogenic survival. Conclusions: We show that TTFields influence DNA-break repair capacity of tumor cells likely by influencing DNA fragment positioning and DNA strand break ligation thus sensitizing tumor cells to IR. Author Disclosure: K. Zielinska-Chomej: None. M. Giladi: A. Employee; Novocure. A. Tichon: A. Employee; Novocure. J. Tu: None. R. Schneiderman: A. Employee; Novocure. K. Viktorsson: None. E. Kirson: A. Employee; Novocure. Y. Palti: K. Advisory Board; Novocure. M. Stock; Novocure. R. Lewensohn: None." @default.
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- W2100054331 date "2014-09-01" @default.
- W2100054331 modified "2023-09-26" @default.
- W2100054331 title "DNA Damage Response During Mitosis Induces Cancer Chromosomal Instability" @default.
- W2100054331 doi "https://doi.org/10.1016/j.ijrobp.2014.05.2257" @default.
- W2100054331 hasPublicationYear "2014" @default.
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