Tsuboi K, Tsuchida Y, Nose T, Ando K
Department of Neurological Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan.
Int J Radiat Biol. 1998 Jul;74(1):71-9. doi: 10.1080/095530098141744.
The cytotoxic effect of high-LET carbon beams was analysed on p53 mutant and wild-type glioblastoma cell lines.
Three glioblastoma (U251MG, TK-1, A-172) cell lines, one medulloblastoma (ONS-76) and one fibroblast cell line (NB1RGB) were used. U251MG and TK-1 have mutated p53, A-172, ONS-76 and NB1RGB have wild-type p53. Gamma-ray and 290 MeV/u carbon mono-peak beams with average LET values of 20, 40, 81 and 105keV/microm were used. Cytotoxicity was measured by clonogenic survival assay and DNA histograms were analysed by flow cytometry.
The RBE values for carbon beams at D10 ranged from approximately 1.5-1.7 (20keV) to 2.9-3.1 (105keV). Although p53 mutants were more resistant than wild-types for all radiation qualities, carbon beams yielded a higher RBE in p53 mutants than in wild-types. Alpha values were significantly smaller in p53 mutants than wild-types for gamma- and 20 keV/microm radiations, while no significant difference was noticed for LET greater than 40 keV/microm. A G1 block was noticed after irradiation with gamma-rays and carbon beams of 20 and 40keV/microm in p53 wild-types. A more pronounced G2 block occurred in p53 mutants than wild-types in proportion to LET up to 105 keV/microm.
Accelerated carbon beams can yield higher RBE in gamma-resistant glioblastoma cell lines with p53 mutations. High-LET irradiation induces not only disappearance of the p53-dependent G1 block but also a greater G2 block in glioblastoma cell lines.
分析高传能线密度碳离子束对p53突变型和野生型胶质母细胞瘤细胞系的细胞毒性作用。
使用了三种胶质母细胞瘤（U251MG、TK-1、A-172）细胞系、一种髓母细胞瘤（ONS-76）和一种成纤维细胞系（NB1RGB）。U251MG和TK-1的p53发生了突变，A-172、ONS-76和NB1RGB具有野生型p53。使用了平均传能线密度值为20、40、81和105keV/μm的γ射线和290MeV/u碳单能峰束。通过克隆形成存活试验测量细胞毒性，并通过流式细胞术分析DNA直方图。
碳离子束在D10时的相对生物效应值范围约为1.5 - 1.7（20keV）至2.9 - 3.1（105keV）。尽管对于所有辐射质量，p53突变体比野生型更具抗性，但碳离子束在p53突变体中产生的相对生物效应高于野生型。对于γ射线和20keV/μm辐射，p53突变体的α值显著小于野生型，而当传能线密度大于40keV/μm时未观察到显著差异。在p53野生型细胞中，用γ射线以及20和40keV/μm的碳离子束照射后观察到G1期阻滞。在传能线密度高达105keV/μm时，p53突变体中比野生型出现更明显的G2期阻滞。
加速碳离子束在具有p53突变的抗γ射线胶质母细胞瘤细胞系中可产生更高的相对生物效应。高传能线密度辐射不仅诱导胶质母细胞瘤细胞系中p53依赖的G1期阻滞消失，还诱导更大程度的G2期阻滞。
