同一解剖部位和组织学类型的细胞系在固有放射敏感性和对质子和碳离子的相对生物学效应方面表现出很大的可变性。
Cell lines of the same anatomic site and histologic type show large variability in intrinsic radiosensitivity and relative biological effectiveness to protons and carbon ions.
机构信息
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
出版信息
Med Phys. 2021 Jun;48(6):3243-3261. doi: 10.1002/mp.14878. Epub 2021 May 9.
PURPOSE
To show that intrinsic radiosensitivity varies greatly for protons and carbon (C) ions in addition to photons, and that DNA repair capacity remains important in governing this variability.
METHODS
We measured or obtained from the literature clonogenic survival data for a number of human cancer cell lines exposed to photons, protons (9.9 keV/μm), and C-ions (13.3-77.1 keV/μm). We characterized their intrinsic radiosensitivity by the dose for 10% or 50% survival (D or D ), and quantified the variability at each radiation quality by the coefficient of variation (COV) in D and D . We also treated cells with DNA repair inhibitors prior to irradiation to assess how DNA repair capacity affects their variability.
RESULTS
We found no statistically significant differences in the COVs of D or D between any of the radiation qualities investigated. The same was true regardless of whether the cells were treated with DNA repair inhibitors, or whether they were stratified into histologic subsets. Even within histologic subsets, we found remarkable differences in radiosensitivity for high LET C-ions that were often greater than the variations in RBE, with brain cancer cells varying in D (D ) up to 100% (131%) for 77.1 keV/μm C-ions, and non-small cell lung cancer and pancreatic cancer cell lines varying up to 55% (76%) and 51% (78%), respectively, for 60.5 keV/μm C-ions. The cell lines with modulated DNA repair capacity had greater variability in intrinsic radiosensitivity across all radiation qualities.
CONCLUSIONS
Even for cell lines of the same histologic type, there are remarkable variations in intrinsic radiosensitivity, and these variations do not differ significantly between photon, proton or C-ion radiation. The importance of DNA repair capacity in governing the variability in intrinsic radiosensitivity is not significantly diminished for higher LET radiation.
目的
除了光子外，还表明质子和碳（C）离子的固有放射敏感性差异很大，并且 DNA 修复能力在控制这种变异性方面仍然很重要。
方法
我们测量了或从文献中获得了许多暴露于光子、质子（9.9 keV/μm）和 C 离子（13.3-77.1 keV/μm）的人类癌细胞系的集落形成存活数据。我们通过 10%或 50%存活的剂量（D 或 D ）来表征它们的固有放射敏感性，并通过 D 和 D 的变异系数（COV）来量化每种辐射质量的变异性。我们还在照射前用 DNA 修复抑制剂处理细胞，以评估 DNA 修复能力如何影响它们的变异性。
结果
我们发现，在所研究的任何辐射质量之间，D 或 D 的 COV 没有统计学上的显著差异。无论细胞是否用 DNA 修复抑制剂处理，或者是否分为组织学亚组，情况都是如此。即使在组织学亚组内，我们也发现了高传能线密度（LET）C 离子的固有放射敏感性的显著差异，这些差异通常大于相对生物效应（RBE）的变化，脑癌细胞的 D（D ）对于 77.1 keV/μm C 离子变化高达 100%（131%），非小细胞肺癌和胰腺癌细胞系分别高达 55%（76%）和 51%（78%），对于 60.5 keV/μm C 离子。具有调制 DNA 修复能力的细胞系在所有辐射质量下的固有放射敏感性变异性更大。
结论
即使对于同一组织学类型的细胞系，也存在显著的固有放射敏感性差异，并且这些差异在光子、质子或 C 离子辐射之间没有显著差异。在更高 LET 辐射下，DNA 修复能力在控制固有放射敏感性变异性方面的重要性并没有明显降低。
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