Effects of indirect actions and oxygen on relative biological effectiveness: estimate of DSB inductions and conversions induced by therapeutic proton beams

Abstract

Purpose: This study evaluated the DNA double strand breaks (DSBs) induced by indirect actions and its misrepairs to estimate the relative biological effectiveness (RBE) of proton beams.

Materials and methods: From experimental data, DSB induction was evaluated in cells irradiated by 62 MeV proton beams in the presence of dimethylsulphoxide (DMSO) and under hypoxic conditions. The DNA damage yields for calculating the RBE were estimated using Monte Carlo Damage Simulation (MCDS) software. The repair outcomes (correct repairs, mutations and DSB conversions) were estimated using Monte Carlo Excision Repair (MCER) simulations.

Results: The values for RBE of 62 MeV protons (LET = 1.051 keV/μm) for DSB induction and enzymatic DSB under aerobic condition (21% O₂) was 1.02 and 0.94, respectively, as comparing to ⁶⁰Co γ-rays (LET = 2.4 keV/μm). DMSO mitigated the inference of indirect action and reduced DSB induction to a greater extent when damaged by protons rather than γ-rays, resulting in a decreased RBE of 0.86. DMSO also efficiently prevented enzymatic DSB yields triggered by proton irradiation and reduced the RBE to 0.83. However, hypoxia (2% O₂) produced a similar level of DSB induction with respect to the protons and γ-rays, with a comparable RBE of 1.02.

Conclusions: The RBE values of proton beams estimated from DSB induction and enzymatic DSB decreased by 16% and 12%, respectively, in the presence of DMSO. Our findings indicate that the overall effects of DSB induction and enzymatic DSB could intensify the tumor killing, while alleviate normal tissue damage when indirect actions are effectively interrupted.

Keywords:

• Base excision repair
• indirect action
• relative biological effectiveness
• proton therapy
• enzymatic DSB

Acknowledgments

The authors thank Dr. Pankaj Chaudhary of Queen’s University Belfast, Belfast, United Kingdom for providing information on DSB induction in the presence of DMSO. The authors thank Dr. Robert Stewart of University of Washington, Seattle, United States of America for providing information on the CHMX parameter employed in the MCDS and MCER simulations.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This research was funded by grants CSMU-INT-105-0,6 supported by Chung Shan Medical University, Taichung, Taiwan; CSH-2016-A-009, supported by Chung Shan Medical University Hospital, Taichung, Taiwan awarded to Ya-Yun Hsiao; CMRPD1H0472 supported by Linkou-Chang Gung Memorial Hospital; and MOST 107-2314-B-182-068 -MY2 supported by the Ministry of Sciences and Technology in Taiwan, awarded to Fang-Hsin Chen.

Notes on contributors

Wei-Ren Luo

Wei-Ren Luo, is a Radiologist of Chung Shan Medical University Hospital, Taichung, Taiwan. He is a researcher in the field of radiological sciences and radiation protection.

Fang-Hsin Chen

Fang-Hsin Chen, PhD, is an Assistant Professor of Department of Medical Imaging and Radiological Sciences and Department of Radiation Oncology, Chang Gung University, Kweishan, Taiwan and of Radiation Biology Research Center, Institute for Radiological Research, Chang Gung Memorial Hospital, Linkou, Taiwan.

Ren-Jing Huang

Ren-Jing Huang, PhD, is an Associate Professor of Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan. He is a researcher in the field of radiological sciences and sleep medicine.

Yu-Pin Chen

Yu-Pin Chen, MS, is a Radiologist of Department of Radiology, Taipei Manicipal Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan. He is a researcher in the field of radiological sciences and sleep medicine.

Ya-Yun Hsiao

Ya-Yun Hsiao, PhD, is an Assistant Professor of Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan. She is a researcher in the field of radiological sciences and radiation protection.