title: 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 (60)Co 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.
authors.affiliation: Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Ju-Ying
authors.initials: JY
authors.lastname: Tsai
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chang Gung University, Kweishan, Taiwan, Republic of China Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan, Republic of China.
authors.forename: Fang-Hsin
authors.initials: FH
authors.lastname: Chen
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N Road, Taichung, 402, Taiwan, Republic of China.
authors.forename: Tsung-Yu
authors.initials: TY
authors.lastname: Hsieh
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N Road, Taichung, 402, Taiwan, Republic of China yhsiao@csmu.edu.tw.
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Hsiao
mesh_terms: D003198:Computer Simulation; D004249:DNA Damage / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D020450:Heavy Ions; D006371:Helium; D006801:Humans; D007477:Ions; D018499:Linear Energy Transfer / Q000502:physiology / Q000528:radiation effects; D008954:Models, Biological; D015233:Models, Statistical; D010100:Oxygen / Q000378:metabolism*; D012062:Relative Biological Effectiveness
chemical_list: D007477:Ions; D006371:Helium; D010100:Oxygen
keywords: base excision repair; clustered DNA damage; enzymatic DSB; indirect action; relative biological effectiveness