Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Oncol Rep. 2012 Nov;28(5):1591-6. doi: 10.3892/or.2012.1982. Epub 2012 Aug 22.
Charged particle therapy utilizing protons or carbon ions has been rapidly intensifying over recent years. The present study was designed to jointly investigate these two charged particle treatment modalities with respect to modeled anatomical depth-dependent dose and linear energy transfer (LET) deliveries to cells with either normal or compromised DNA repair phenotypes. We compared cellular lethality in response to dose, LET and Bragg peak location for accelerated protons and carbon ions at 70 and 290 MeV/n, respectively. A novel experimental live cell irradiation OptiCell™ in vitro culture system using three different Chinese hamster ovary (CHO) cells as a mammalian model was conducted. A wild-type DNA repair-competent CHO cell line (CHO 10B2) was compared to two other CHO cell lines (51D1 and xrs5), each genetically deficient with respect to one of the two major DNA repair pathways (homologous recombination and non-homologous end joining pathways, respectively) following genotoxic insults. We found that wild-type and homologous recombination-deficient (Rad51D) cellular lethality was dependent on both the dose and LET of the carbon ions, whereas it was only dependent on dose for protons. The non-homologous end joining deficient cell line (Ku80 mutant) showed nearly identical dose-response profiles for both carbon ions and protons. Our results show that the increasingly used modality of carbon ions as charged particle therapy is advantageous to protons in a radiotherapeutic context, primarily for tumor cells proficient in non-homologous end joining DNA repair where cellular lethality is dependent not only on the dose as in the case of more common photon therapeutic modalities, but more importantly on the carbon ion LETs. Genetic characterization of patient tumors would be key to individualize and optimize the selection of radiation modality, clinical outcome and treatment cost.
近年来，利用质子或碳离子进行的带电荷粒子治疗得到了迅速发展。本研究旨在联合研究这两种带电荷粒子治疗方式，针对正常或 DNA 修复功能受损的细胞，研究模型解剖深度相关的剂量和线性能量传递（LET）分布。我们比较了分别以 70 MeV/n 和 290 MeV/n 加速的质子和碳离子，在剂量、LET 和布拉格峰位置方面对细胞的致死率。采用新型的活细胞照射 OptiCell™体外培养系统，使用三种不同的中国仓鼠卵巢（CHO）细胞作为哺乳动物模型进行实验。将具有野生型 DNA 修复功能的 CHO 细胞系（CHO 10B2）与另外两种 CHO 细胞系（51D1 和 xrs5）进行比较，后两者在受到遗传毒性损伤后，分别在两种主要的 DNA 修复途径（同源重组和非同源末端连接途径）中的一条途径中存在遗传缺陷。我们发现，野生型和同源重组缺陷型（Rad51D）细胞的致死率既依赖于碳离子的剂量，又依赖于 LET，而对于质子，仅依赖于剂量。非同源末端连接缺陷型细胞系（Ku80 突变体）对碳离子和质子表现出几乎相同的剂量反应曲线。我们的结果表明，在放射治疗方面，作为带电荷粒子治疗的日益使用的模态碳离子比质子更有优势，主要是针对非同源末端连接 DNA 修复功能良好的肿瘤细胞，因为细胞致死率不仅取决于剂量，就像更常见的光子治疗模式一样，而且更重要的是取决于碳离子 LET。对肿瘤患者的遗传特征进行分析是实现个体化和优化辐射方式选择、临床结局和治疗成本的关键。
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