Repair protein damage vs. cell repair saturation : a comparison of its use in radiobiological models

Mingo Barba, Sergio; Lattuada, Marco; Füchslin, Rudolf Marcel; Fink, Alke; Scheidegger, Stephan

Publication type:	Conference poster
Type of review:	Peer review (abstract)
Title:	Repair protein damage vs. cell repair saturation : a comparison of its use in radiobiological models
Authors:	Mingo Barba, Sergio Lattuada, Marco Füchslin, Rudolf Marcel Fink, Alke Scheidegger, Stephan
et. al:	No
Conference details:	26th Annual SASRO Meeting, Baden, Switzerland, 1-3 September 2022
Issue Date:	2022
Language:	English
Subjects:	Repair dynamics; Radiation biophysics
Subject (DDC):	616: Internal medicine and diseases
Abstract:	Aims: Most of the actual radiobiological models consider only DNA as target of study. But other cellular elements may also have a capital role for survival, e.g. the availability and/or efficiency of repair proteins. Consequently, they should be covered by models as well. There are different hypotheses about how repair proteins can be affected by radiation, but none of them is sufficiently corroborated by experimental studies. This work compares the ability to explain diverse radiobiological effects of two hypothetical mechanisms: protein radiation-induced damage and cell repair saturation. Methods: We used the Multi-Hit Repair (MHR) model. In its original formulation, it already included a radiation-induced protein damage mechanism. With protein damage, the MHR-model exhibits a proven capability to cover experimental data from different biological tests such as clonogenic - and comet assay. We compared these results with those from a formulation in which protein damage is substituted by saturation of repair proteins. In order to obtain a repair-saturated mechanism, Michaelis-Menten kinetics were introduced in the repair function of the MHR model. Results: Both protein-related models were able to explain radiobiological effects as linear-quadratic-linear (LQL) survival curves or dose-rate survival effects like exponential survival curves at low dose rates (~0.01 Gy/min) or the increase of the survival with the reduction of the dose-rate in the range of 0.1-2 Gy/min. Conclusion: Due to the previously mentioned lack of experimental data in this field, it is impossible to decide which of these two protein mechanisms is closer to reality. However, the repair saturation mechanism simplifies the MHR model because it works with one parameter less than in its original formulation, which could be essential because of the problems encountered in the past to obtain a proper model calibration. The ability of the proposed repair saturation mechanism to cover essential aspects such as dose-rate dependence and LQL-behaviour of survival indicates that it constitutes an alternative explanation to the repair protein damage mechanism for radiation used in the original MHR model.
URI:	https://digitalcollection.zhaw.ch/handle/11475/30885
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	School of Engineering
Organisational Unit:	Institute of Applied Mathematics and Physics (IAMP)
Published as part of the ZHAW project:	Hyperboost
Appears in collections:	Publikationen School of Engineering

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Mingo Barba, S., Lattuada, M., Füchslin, R. M., Fink, A., & Scheidegger, S. (2022). Repair protein damage vs. cell repair saturation : a comparison of its use in radiobiological models. 26th Annual SASRO Meeting, Baden, Switzerland, 1-3 September 2022.

Mingo Barba, S. et al. (2022) ‘Repair protein damage vs. cell repair saturation : a comparison of its use in radiobiological models’, in 26th Annual SASRO Meeting, Baden, Switzerland, 1-3 September 2022.

S. Mingo Barba, M. Lattuada, R. M. Füchslin, A. Fink, and S. Scheidegger, “Repair protein damage vs. cell repair saturation : a comparison of its use in radiobiological models,” in 26th Annual SASRO Meeting, Baden, Switzerland, 1-3 September 2022, 2022.

MINGO BARBA, Sergio, Marco LATTUADA, Rudolf Marcel FÜCHSLIN, Alke FINK und Stephan SCHEIDEGGER, 2022. Repair protein damage vs. cell repair saturation : a comparison of its use in radiobiological models. In: 26th Annual SASRO Meeting, Baden, Switzerland, 1-3 September 2022. Conference poster. 2022

Mingo Barba, Sergio, Marco Lattuada, Rudolf Marcel Füchslin, Alke Fink, and Stephan Scheidegger. 2022. “Repair Protein Damage vs. Cell Repair Saturation : A Comparison of Its Use in Radiobiological Models.” Conference poster. In 26th Annual SASRO Meeting, Baden, Switzerland, 1-3 September 2022.

Mingo Barba, Sergio, et al. “Repair Protein Damage vs. Cell Repair Saturation : A Comparison of Its Use in Radiobiological Models.” 26th Annual SASRO Meeting, Baden, Switzerland, 1-3 September 2022, 2022.