PMID- 31682784 OWN - NLM STAT- MEDLINE DCOM- 20200423 LR - 20200423 IS - 1362-3095 (Electronic) IS - 0955-3002 (Linking) VI - 96 IP - 2 DP - 2020 Feb TI - Effects of indirect actions and oxygen on relative biological effectiveness: estimate of DSB inductions and conversions induced by therapeutic proton beams. PG - 187-196 LID - 10.1080/09553002.2020.1688883 [doi] AB - 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/mum) for DSB induction and enzymatic DSB under aerobic condition (21% O(2)) was 1.02 and 0.94, respectively, as comparing to (60)Co gamma-rays (LET = 2.4 keV/mum). DMSO mitigated the inference of indirect action and reduced DSB induction to a greater extent when damaged by protons rather than gamma-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% O(2)) produced a similar level of DSB induction with respect to the protons and gamma-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. FAU - Luo, Wei-Ren AU - Luo WR AD - Department of Radiology, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Chen, Fang-Hsin AU - Chen FH AUID- ORCID: 0000-0002-1671-4863 AD - Department of Medical Imaging and Radiological Sciences, Chang Gung University, Kweishan, Taiwan. AD - Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Taoyuan, Taiwan. AD - Department of Radiation Oncology, Chang Gung Memorial Hospital-Linkou Branch, Taoyuan, Taiwan. FAU - Huang, Ren-Jing AU - Huang RJ AD - Department of Radiology, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan. FAU - Chen, Yu-Pin AU - Chen YP AD - Department of Radiology, Taipei Manicipal Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan. FAU - Hsiao, Ya-Yun AU - Hsiao YY AUID- ORCID: 0000-0001-7494-8767 AD - Department of Radiology, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191113 PL - England TA - Int J Radiat Biol JT - International journal of radiation biology JID - 8809243 RN - 0 (Cobalt Radioisotopes) RN - 0 (Protons) RN - 0 (Reactive Oxygen Species) RN - 9007-49-2 (DNA) RN - S88TT14065 (Oxygen) RN - YOW8V9698H (Dimethyl Sulfoxide) SB - IM MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Cobalt Radioisotopes MH - DNA/*radiation effects MH - *DNA Breaks, Double-Stranded MH - DNA Repair/radiation effects MH - Dimethyl Sulfoxide MH - Gamma Rays MH - Humans MH - Hypoxia MH - Monte Carlo Method MH - Mutation MH - Oxygen/*metabolism MH - Proton Therapy/*methods MH - Protons MH - Reactive Oxygen Species/metabolism MH - *Relative Biological Effectiveness OTO - NOTNLM OT - Base excision repair OT - enzymatic DSB OT - indirect action OT - proton therapy OT - relative biological effectiveness EDAT- 2019/11/05 06:00 MHDA- 2020/04/24 06:00 CRDT- 2019/11/05 06:00 PHST- 2019/11/05 06:00 [pubmed] PHST- 2020/04/24 06:00 [medline] PHST- 2019/11/05 06:00 [entrez] AID - 10.1080/09553002.2020.1688883 [doi] PST - ppublish SO - Int J Radiat Biol. 2020 Feb;96(2):187-196. doi: 10.1080/09553002.2020.1688883. Epub 2019 Nov 13.