Prediction of DNA rejoining kinetics and cell survival after proton irradiation for V79 cells using Geant4-DNA

Authors

Dousatsu Sakata, National Institutes for Quantum Science and Technology
Ryoichi Hirayama, National Institutes for Quantum Science and Technology
Wook Geun Shin, Seoul National University Hospital
Mauro Belli
Maria A. Tabocchini, Istituto Nazionale di Fisica Nucleare - INFN
Robert D. Stewart, University of Washington
Oleg Belov, Joint Institute for Nuclear Research, Dubna
Mario A. Bernal, Universidade Estadual de Campinas
Marie Claude Bordage, Centre de Recherches en Cancérologie de Toulouse
Jeremy M.C. Brown, Swinburne University of Technology
Milos Dordevic, Institut za Nuklearne Nauke Vinca
Dimitris Emfietzoglou, University of Ioannina
Ziad Francis, Université Saint-Joseph de Beyrouth
Susanna Guatelli, University of Wollongong
Taku Inaniwa, National Institutes for Quantum Science and Technology
Vladimir Ivanchenko, Geant4 Associates International Ltd.
Mathieu Karamitros
Ioanna Kyriakou, University of Ioannina
Nathanael Lampe
Zhuxin Li, LP2I - Laboratoire de Physique des Deux Infinis Bordeaux
Sylvain Meylan
Claire Michelet, LP2I - Laboratoire de Physique des Deux Infinis Bordeaux
Petteri Nieminen, ESTEC - European Space Research and Technology Centre
Yann Perrot, IRSN Institut de Radioprotection et de Sureté Nucléaire
Ivan Petrovic, Institut za Nuklearne Nauke Vinca
Jose Ramos-Mendez, University of California, San Francisco
Aleksandra Ristic-Fira, Institut za Nuklearne Nauke Vinca
Giovanni Santin, ESTEC - European Space Research and Technology Centre
Jan Schuemann, Massachusetts General Hospital

Publication Name

Physica Medica

Abstract

Purpose: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology. Methods: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs. Results: By optimizing the model parameters of the TLK model in accordance to the experimental data on V79, we were able to predict both DNA rejoining kinetics at low linear energy transfers (LET) and cell surviving fraction. Conclusion: This is the first study to demonstrate the implementation of both the cell surviving fraction and the DNA rejoining kinetics with the estimated initial DNA damage, in a realistic cell geometrical model simulated by full track structure MC simulations at DNA level and for various LET. These simulation and model make the link between mechanistic physical/chemical damage processes and these two specific biological endpoints.

Open Access Status

This publication may be available as open access

Volume

105

Article Number

102508

Funding Number

DP170100967

Funding Sponsor

National Institutes of Health

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Link to publisher version (DOI)

http://dx.doi.org/10.1016/j.ejmp.2022.11.012