Development of computational model for cell dose and DNA damage quantification of multicellular system

Abstract

Purpose: The aim of this study is to build a computational model to investigate the cell dose and cell DNA damage distribution of a multicellular tissue system under the irradiation.

Materials and methods: In this work, we developed a computational model for quantifying cell dose and double strand break (DSB) number in a multicellular system by simulating the radiation transport in 2D and 3D cell culture. The model was based on an open-source radiation transport package, Geant4 with Geant4-DNA physics. First, the computational multicellular system was created using a developed program, CelllMaker. Second, the radiation transport simulation for cells was conducted using Geant4 package with the Geant4-DNA physics to obtain the cellular dose and cellular DSB yield.

Results: Using the method described in this work, it is possible to obtain the cellular dose and DNA damage simultaneously. The developed model provides a solution for quantifying the cellular dose and cellular DNA damage which are not easily determined in a radiobiological experiment.

Conclusions: With limited validation data for the model, this preliminary study provides a roadmap for building a comprehensive toolkit for simulating cellular dose and DNA damage of multicellular tissue systems.

Keywords:

• Geant4
• Geant4-DNA
• multicellular model
• cellular dose
• DNA damage
• computational model
• Monte Carlo simulation

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This study was supported by Consortium for Risk Evaluation and Stakeholder Participation (http://www.cresp.org).

Notes on contributors

Ruirui Liu

Ruirui Liu, PhD, is a Postdoc Research Associate at the Department of Radiation Oncology of Washington University in Saint Louis (WashU). Dr. Liu's research interests include computational radiation biology, computational medical physics and proton therapy.

Tianyu Zhao

Tianyu Zhao, PhD, is an Assistant Professor of radiation oncology (WashU) and co-chief of Proton Therapy Physics service. Dr. Zhao's research interests include proton therapy and adaptive radiotherapy.

Maciej H. Swat

Maciej H. Swat, PhD, in a Research Associate of biocomplexity institute at Indiana University. Dr. Swat' s research interests include in large-scale software development and documentation, data processing and mining, project management and scientific programming. Dr. Swat lead CompuCell3D project, a platform for multi-scale biomedical modeling of tissues and organs.

Francisco J. Reynoso

Francisco J. Reynoso, PhD, is an Instructor of Radiation Oncology (WashU). Dr. Reynoso's current research interests include Monte Carlo modeling, nanoparticle-aided radiation dose enhancement and translational clinical research. He currently focuses his clinical duties on SBRT/SRS treatment and brachytherapy.

Kathryn A. Higley

Kathryn A. Higley, PhD, is a Professor of School of Nuclear Science and Technology at Oregon State University. Dr. Higley's fields of interest include environmental transport and fate of radionuclides, radioecology, radiochemistry, radiation dose assessment, neutron activation analysis, nuclear emergency response, and environmental regulations.