Effects of indirect actions and oxygen on relative biological effectiveness: estimate of DSB induction and conversion induced by gamma rays and helium ions

Abstract

Clustered DNA damage other than double-strand breaks (DSBs) can be detrimental to cells and can lead to mutagenesis or cell death. In addition to DSBs induced by ionizing radiation, misrepair of non-DSB clustered damage contributes extra DSBs converted from DNA misrepair via pathways for base excision repair and nucleotide excision repair. This study aimed to quantify the relative biological effectiveness (RBE) when DSB induction and conversion from non-DSB clustered damage misrepair were used as biological endpoints. The results showed that both linear energy transfer (LET) and indirect action had a strong impact on the yields for DSB induction and conversion. RBE values for DSB induction and maximum DSB conversion of helium ions (LET = 120 keV/μm) to 60Co gamma rays were 3.0 and 3.2, respectively. These RBE values increased to 5.8 and 5.6 in the absence of interference of indirect action initiated by addition of 2-M dimethylsulfoxide. DSB conversion was ∼1–4% of the total non-DSB damage due to gamma rays, which was lower than the 10% estimate by experimental measurement. Five to twenty percent of total non-DSB damage due to helium ions was converted into DSBs. Hence, it may be possible to increase the yields of DSBs in cancerous cells through DNA repair pathways, ultimately enhancing cell killing.

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

“…This study evaluated the DSB induction and repair outcomes in the presence of DMSO and/or under hypoxia. The MCDS-derived results for DSB induction for low- and high-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 ]. Recent experimental data showed that the yields for DSB induction in WiDr (human colon carcinoma) cells irradiated with 6 MV X-rays in the presence of 0.28 M DMSO decreased to 62% using pulse-field gel electrophoresis assay [ 22 ] while MCDS simulation showed that the DSB yields reduced to 54%.…”

“…In RT, the use of dimethylsulfoxide (DMSO) as a ROS scavenger reduces the yields of DSB induction for both low and high-LET radiations [ 21 ] and increases cell survival [ 22 , 23 ]. Monte Carlo simulations and experiments also demonstrated that DMSO reduces the mutation frequency and increases the probability of correct repair [ 24 , 25 ]. Besides, DMSO can be used in RT to reduce the side effects [ 26 ].…”

The Role of Hypoxia and SRC Tyrosine Kinase in Glioblastoma Invasiveness and Radioresistance

“…LET is a measure of ionization density and it is defined as the average energy (keV) transferred by a particle along the 1 μm path [ 89 ]. High LET particles show high ionization density, thus inducing increased direct cell damage, but display lower indirect effects mediated by ROS and other radicals [ 89 , 90 ]. Another main advantage of particle-based radiation therapy is the finite dose deposition in the tissue that allows sparing the normal brain tissue.…”

Faculty Opinions recommendation of The role of hypoxia and SRC tyrosine kinase in glioblastoma invasiveness and radioresistance.

“…LET is a measure of ionization density and it is defined as the average energy (keV) transferred by a particle along the 1 µm path [89]. High LET particles show high ionization density, thus inducing increased direct cell damage, but display lower indirect effects mediated by ROS and other radicals [89,90]. Another main advantage of particle-based radiation therapy is the finite dose deposition in the tissue that allows sparing the normal brain tissue.…”