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Open AccessArticle

Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation

by Hans Liew 1,2,3,4,5,6, Carmen Klein 2,3,4,5, Frank T. Zenke 7, Amir Abdollahi 2,3,4,5, Jürgen Debus 1,2,3,4,5,6, Ivana Dokic 2,3,4,5,*,† and Andrea Mairani 2,3,4,5,*,†
1
Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
2
Division of Molecular and Translational Radiation Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, 69120 Heidelberg, Germany
3
Heidelberg Institute of Radiation Oncology (HIRO), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
4
German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
5
Heidelberg Ion-Beam Therapy Center (HIT), 69120 Heidelberg, Germany
6
Faculty of Physics and Astronomy, Heidelberg University, 69120 Heidelberg, Germany
7
Merck KGaA, 64293 Darmstadt, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(23), 6054; https://doi.org/10.3390/ijms20236054
Received: 24 October 2019 / Revised: 26 November 2019 / Accepted: 28 November 2019 / Published: 30 November 2019
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells)
Mechanistic approaches to modeling the effects of ionizing radiation on cells are on the rise, promising a better understanding of predictions and higher flexibility concerning conditions to be accounted for. In this work we modified and extended a previously published mechanistic model of cell survival after photon irradiation under hypoxia to account for radiosensitization caused by deficiency or inhibition of DNA damage repair enzymes. The model is shown to be capable of describing the survival data of cells with DNA damage repair deficiency, both under norm- and hypoxia. We find that our parameterization of radiosensitization is invariant under change of oxygen status, indicating that the relevant parameters for both mechanisms can be obtained independently and introduced freely to the model to predict their combined effect. View Full-Text
Keywords: ionizing radiation; DNA repair; hypoxia; modeling; radiosensitizer ionizing radiation; DNA repair; hypoxia; modeling; radiosensitizer
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Liew, H.; Klein, C.; Zenke, F.T.; Abdollahi, A.; Debus, J.; Dokic, I.; Mairani, A. Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation. Int. J. Mol. Sci. 2019, 20, 6054.

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