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  • Sir Peter MacCallum Department of Oncology
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    Monitoring DNA Damage and Repair in Peripheral Blood Mononuclear Cells of Lung Cancer Radiotherapy Patients

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    Author
    Lobachevsky, PN; Bucknell, NW; Mason, J; Russo, D; Yin, X; Selbie, L; Ball, DL; Kron, T; Hofman, M; Siva, S; ...
    Date
    2020-09-01
    Source Title
    Cancers
    Publisher
    MDPI
    University of Melbourne Author/s
    Kron, Tomas
    Affiliation
    Sir Peter MacCallum Department of Oncology
    Metadata
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    Document Type
    Journal Article
    Citations
    Lobachevsky, P. N., Bucknell, N. W., Mason, J., Russo, D., Yin, X., Selbie, L., Ball, D. L., Kron, T., Hofman, M., Siva, S. & Martin, O. A. (2020). Monitoring DNA Damage and Repair in Peripheral Blood Mononuclear Cells of Lung Cancer Radiotherapy Patients. CANCERS, 12 (9), https://doi.org/10.3390/cancers12092517.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/251560
    DOI
    10.3390/cancers12092517
    Abstract
    Thoracic radiotherapy (RT) is required for the curative management of inoperable lung cancer, however, treatment delivery is limited by normal tissue toxicity. Prior studies suggest that using radiation-induced DNA damage response (DDR) in peripheral blood mononuclear cells (PBMC) has potential to predict RT-associated toxicities. We collected PBMC from 38 patients enrolled on a prospective clinical trial who received definitive fractionated RT for non-small cell lung cancer. DDR was measured by automated counting of nuclear γ-H2AX foci in immunofluorescence images. Analysis of samples collected before, during and after RT demonstrated the induction of DNA damage in PBMC collected shortly after RT commenced, however, this damage repaired later. Radiation dose to the tumour and lung contributed to the in vivo induction of γ-H2AX foci. Aliquots of PBMC collected before treatment were also irradiated ex vivo, and γ-H2AX kinetics were analyzed. A trend for increasing of fraction of irreparable DNA damage in patients with higher toxicity grades was revealed. Slow DNA repair in three patients was associated with a combined dysphagia/cough toxicity and was confirmed by elevated in vivo RT-generated irreparable DNA damage. These results warrant inclusion of an assessment of DDR in PBMC in a panel of predictive biomarkers that would identify patients at a higher risk of toxicity.

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