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用于光子、中子和轻离子的DNA双链断裂(DSB)相对生物效应(RBE)的快速MCNP模拟

Rapid MCNP simulation of DNA double strand break (DSB) relative biological effectiveness (RBE) for photons, neutrons, and light ions.

作者信息

Stewart Robert D, Streitmatter Seth W, Argento David C, Kirkby Charles, Goorley John T, Moffitt Greg, Jevremovic Tatjana, Sandison George A

机构信息

Department of Radiation Oncology, University of Washington School of Medicine, School of Medicine, 1959 NE Pacific Street, Box 356043, Seattle, WA 98195, USA.

出版信息

Phys Med Biol. 2015 Nov 7;60(21):8249-74. doi: 10.1088/0031-9155/60/21/8249. Epub 2015 Oct 9.

Abstract

To account for particle interactions in the extracellular (physical) environment, information from the cell-level Monte Carlo damage simulation (MCDS) for DNA double strand break (DSB) induction has been integrated into the general purpose Monte Carlo N-particle (MCNP) radiation transport code system. The effort to integrate these models is motivated by the need for a computationally efficient model to accurately predict particle relative biological effectiveness (RBE) in cell cultures and in vivo. To illustrate the approach and highlight the impact of the larger scale physical environment (e.g. establishing charged particle equilibrium), we examined the RBE for DSB induction (RBEDSB) of x-rays, (137)Cs γ-rays, neutrons and light ions relative to γ-rays from (60)Co in monolayer cell cultures at various depths in water. Under normoxic conditions, we found that (137)Cs γ-rays are about 1.7% more effective at creating DSB than γ-rays from (60)Co (RBEDSB  =  1.017) whereas 60-250 kV x-rays are 1.1 to 1.25 times more efficient at creating DSB than (60)Co. Under anoxic conditions, kV x-rays may have an RBEDSB up to 1.51 times as large as (60)Co γ-rays. Fission neutrons passing through monolayer cell cultures have an RBEDSB that ranges from 2.6 to 3.0 in normoxic cells, but may be as large as 9.93 for anoxic cells. For proton pencil beams, Monte Carlo simulations suggest an RBEDSB of about 1.2 at the tip of the Bragg peak and up to 1.6 a few mm beyond the Bragg peak. Bragg peak RBEDSB increases with decreasing oxygen concentration, which may create opportunities to apply proton dose painting to help address tumor hypoxia. Modeling of the particle RBE for DSB induction across multiple physical and biological scales has the potential to aid in the interpretation of laboratory experiments and provide useful information to advance the safety and effectiveness of hadron therapy in the treatment of cancer.

摘要

为了考虑细胞外(物理)环境中的粒子相互作用,来自用于DNA双链断裂(DSB)诱导的细胞水平蒙特卡罗损伤模拟(MCDS)的信息已被整合到通用蒙特卡罗N粒子(MCNP)辐射传输代码系统中。整合这些模型的工作是出于对一种计算效率高的模型的需求,该模型能够准确预测细胞培养物和体内的粒子相对生物效应(RBE)。为了说明该方法并突出更大尺度物理环境的影响(例如建立带电粒子平衡),我们研究了在水的不同深度的单层细胞培养物中,X射线、(137)铯γ射线、中子和轻离子相对于(60)钴γ射线诱导DSB的RBE(RBEDSB)。在常氧条件下,我们发现(137)铯γ射线在产生DSB方面比(60)钴γ射线有效约1.7%(RBEDSB = 1.017),而60 - 250 kV的X射线在产生DSB方面比(60)钴γ射线效率高1.1至1.25倍。在缺氧条件下,kV X射线的RBEDSB可能高达(60)钴γ射线的1.51倍。穿过单层细胞培养物的裂变中子在常氧细胞中的RBEDSB范围为2.6至3.0,但在缺氧细胞中可能高达9.93。对于质子笔形束,蒙特卡罗模拟表明在布拉格峰尖端的RBEDSB约为1.2,在布拉格峰之外几毫米处高达1.6。布拉格峰处的RBEDSB随着氧浓度的降低而增加,这可能为应用质子剂量描绘来帮助解决肿瘤缺氧创造机会。跨多个物理和生物尺度对粒子诱导DSB的RBE进行建模,有可能有助于解释实验室实验,并为提高强子治疗癌症的安全性和有效性提供有用信息。

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