{"title":"The Effects of Particle LET and Fluence on the Complexity and Frequency of Clustered DNA Damage","authors":"M. Rezaee, A. Adhikary","doi":"10.3390/dna4010002","DOIUrl":null,"url":null,"abstract":"Motivation: Clustered DNA-lesions are predominantly induced by ionizing radiation, particularly by high-LET particles, and considered as lethal damage. Quantification of this specific type of damage as a function of radiation parameters such as LET, dose rate, dose, and particle type can be informative for the prediction of biological outcome in radiobiological studies. This study investigated the induction and complexity of clustered DNA damage for three different types of particles at an LET range of 0.5–250 keV/µm. Methods: Nanometric volumes (36.0 nm3) of 15 base-pair DNA with its hydration shell was modeled. Electron, proton, and alpha particles at various energies were simulated to irradiate the nanometric volumes. The number of ionization events, low-energy electron spectra, and chemical yields for the formation of °OH, H°, eaq−, and H2O2 were calculated for each particle as a function of LET. Single- and double-strand breaks (SSB and DSB), base release, and clustered DNA-lesions were computed from the Monte-Carlo based quantification of the reactive species and measured yields of the species responsible for the DNA lesion formation. Results: The total amount of DNA damage depends on particle type and LET. The number of ionization events underestimates the quantity of DNA damage at LETs higher than 10 keV/µm. Minimum LETs of 9.4 and 11.5 keV/µm are required to induce clustered damage by a single track of proton and alpha particles, respectively. For a given radiation dose, an increase in LET reduces the number of particle tracks, leading to more complex clustered DNA damage, but a smaller number of separated clustered damage sites. Conclusions: The dependency of the number and the complexity of clustered DNA damage on LET and fluence suggests that the quantification of this damage can be a useful method for the estimation of the biological effectiveness of radiation. These results also suggest that medium-LET particles are more appropriate for the treatment of bulk targets, whereas high-LET particles can be more effective for small targets.","PeriodicalId":72835,"journal":{"name":"DNA","volume":"34 41","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"DNA","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/dna4010002","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Motivation: Clustered DNA-lesions are predominantly induced by ionizing radiation, particularly by high-LET particles, and considered as lethal damage. Quantification of this specific type of damage as a function of radiation parameters such as LET, dose rate, dose, and particle type can be informative for the prediction of biological outcome in radiobiological studies. This study investigated the induction and complexity of clustered DNA damage for three different types of particles at an LET range of 0.5–250 keV/µm. Methods: Nanometric volumes (36.0 nm3) of 15 base-pair DNA with its hydration shell was modeled. Electron, proton, and alpha particles at various energies were simulated to irradiate the nanometric volumes. The number of ionization events, low-energy electron spectra, and chemical yields for the formation of °OH, H°, eaq−, and H2O2 were calculated for each particle as a function of LET. Single- and double-strand breaks (SSB and DSB), base release, and clustered DNA-lesions were computed from the Monte-Carlo based quantification of the reactive species and measured yields of the species responsible for the DNA lesion formation. Results: The total amount of DNA damage depends on particle type and LET. The number of ionization events underestimates the quantity of DNA damage at LETs higher than 10 keV/µm. Minimum LETs of 9.4 and 11.5 keV/µm are required to induce clustered damage by a single track of proton and alpha particles, respectively. For a given radiation dose, an increase in LET reduces the number of particle tracks, leading to more complex clustered DNA damage, but a smaller number of separated clustered damage sites. Conclusions: The dependency of the number and the complexity of clustered DNA damage on LET and fluence suggests that the quantification of this damage can be a useful method for the estimation of the biological effectiveness of radiation. These results also suggest that medium-LET particles are more appropriate for the treatment of bulk targets, whereas high-LET particles can be more effective for small targets.
动机成簇的 DNA 分裂主要由电离辐射,尤其是高 LET 粒子诱发,被认为是致命的损伤。将这种特定类型的损伤量化为辐射参数(如 LET、剂量率、剂量和粒子类型)的函数,可为放射生物学研究中生物结果的预测提供信息。本研究调查了在 0.5-250 keV/µm 的 LET 范围内,三种不同类型粒子诱导的成簇 DNA 损伤及其复杂性。研究方法对 15 个碱基对 DNA 及其水合外壳的纳米体积(36.0 nm3)进行建模。模拟了不同能量的电子、质子和阿尔法粒子对纳米体积的照射。计算了每种粒子的电离事件数、低能电子能谱以及形成 °OH、H°、eaq- 和 H2O2 的化学产率与 LET 的函数关系。单链和双链断裂(SSB 和 DSB)、碱基释放和簇状 DNA 病变是根据蒙特卡洛反应物的定量和 DNA 病变形成的反应物的测量产率计算得出的。结果显示DNA 损伤的总量取决于粒子类型和 LET。当 LET 超过 10 keV/µm 时,电离事件的数量低估了 DNA 损伤的数量。质子和阿尔法粒子的单一轨道分别需要 9.4 和 11.5 keV/µm 的最小 LET 才能诱发成簇的损伤。在给定的辐射剂量下,LET 的增加会减少粒子轨迹的数量,从而导致更复杂的成簇 DNA 损伤,但分离的成簇损伤位点的数量会减少。结论成簇 DNA 损伤的数量和复杂程度与 LET 和通量的关系表明,对这种损伤进行量化是估算辐射生物有效性的一种有用方法。这些结果还表明,中等 LET 粒子更适合处理大块目标,而高 LET 粒子对小目标更有效。