The Effects of Dimethylsulfoxide and Oxygen on DNA Damage Induction and Repair Outcomes for Cells Irradiated by 62 MeV Proton and 3.31 MeV Helium Ions.

Chun-Chieh Chan,Ya-Yun Hsiao

doi:10.3390/jpm11040286

Abstract

Reactive oxygen species (ROS) play an essential role in radiation-induced indirect actions. In terms of DNA damage, double strand breaks (DSBs) have the greatest effects on the repair of DNA damage, cell survival and transformation. This study evaluated the biological effects of the presence of ROS and oxygen on DSB induction and mutation frequency. The relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) of 62 MeV therapeutic proton beams and 3.31 MeV helium ions were calculated using Monte Carlo damage simulation (MCDS) software. Monte Carlo excision repair (MCER) simulations were used to calculate the repair outcomes (mutation frequency). The RBE values of proton beams decreased to 0.75 in the presence of 0.4 M dimethylsulfoxide (DMSO) and then increases to 0.9 in the presence of 2 M DMSO while the RBE values of 3.31 MeV helium ions increased from 2.9 to 5.7 (0–2 M). The mutation frequency of proton beams also decreased from 0.008–0.065 to 0.004–0.034 per cell per Gy by the addition of 2 M DMSO, indicating that ROS affects both DSB induction and repair outcomes. These results show that the combined use of DMSO in normal tissues and an increased dose in tumor regions increases treatment efficiency.

Highlights

Proton therapy and helium ion therapy have been used in radiation therapy (RT) and have attracted a lot interest owing to their abilities to deliver conformal dose into the tumor area and spare surrounding tissues [1,2]
This study evaluated the double strand breaks (DSBs) induction and repair outcomes in the presence of DMSO and/or under hypoxia
The Monte Carlo damage simulation (MCDS)-derived results for DSB induction for lowand high-linear energy transfer (LET) radiations have been compared with experimental data and track structure simulations elsewhere [38,39,40,45,47,48], including the data for the presence of DMSO or under hypoxia [24,25]

Summary

Introduction

Proton therapy and helium ion therapy have been used in radiation therapy (RT) and have attracted a lot interest owing to their abilities to deliver conformal dose into the tumor area and spare surrounding tissues [1,2] This advantage is associated with the “Bragg curve”, by which the absorbed dose increases very gradually and suddenly rise to a peak at the end of the track [3]. ROS such as hydroxyl radicals and superoxide (O2 − ) can cause clustered DNA damage [7,8,9,10], which can be defined as DNA lesions generated by a single track of ionizing radiation [11]. Among all types of DNA damage, DSB is probably a critical form of DNA damage and serves as the principle determinant of cell death [4,13]

Methods

Results

Conclusion