Format

Send to

Choose Destination
Int J Mol Sci. 2019 Nov 30;20(23). pii: E6054. doi: 10.3390/ijms20236054.

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

Liew H1,2,3,4,5,6, Klein C2,3,4,5, Zenke FT7, Abdollahi A2,3,4,5, Debus J1,2,3,4,5,6, Dokic I2,3,4,5, Mairani A2,3,4,5.

Author information

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.

Abstract

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.

KEYWORDS:

DNA repair; hypoxia; ionizing radiation; modeling; radiosensitizer

Conflict of interest statement

Amir Abdollahi and J├╝rgen Debus received research funds from Merck KGaA, Darmstadt, Germany, and are involved as academic mentors in the DNA-Repair Cluster initiative with Merck KGaA-BioMedX. Frank T. Zenke is an employee of Merck KGaA, Darmstadt, Germany. The other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center