Williams Jerry R, Zhang Yonggang, Zhou Haoming, Gridley Daila S, Koch Cameron J, Slater James M, Little John B
Molecular Radiation Biology Program, Department of Radiation Medicine, Loma Linda Medical Center, Loma Linda, CA, USA.
Int J Radiat Oncol Biol Phys. 2008 Nov 1;72(3):909-17. doi: 10.1016/j.ijrobp.2008.06.1928.
We compared clonogenic survival in 27 human tumor cell lines that vary in genotype after low-dose-rate (LDR) or high-dose rate (HDR) irradiation. We measured susceptibility to LDR-induced redistribution in the cell cycle in eight of these cell lines.
We measured clonogenic survival after up to 96 hours of LDR (0.25 Gy/h) irradiation. We compared these with clonogenic survival after HDR irradiation (50 Gy/h). Using flow cytometry, we measured LDR-induced redistribution as a function of time during LDR irradiation in eight of these cell lines.
Coefficients that describe clonogenic survival after both LDR and HDR irradiation segregate into four radiosensitivity groups that associate with cell genotype: mutant (mut)ATM, wild-type TP53, mutTP53, and an unidentified gene in radioresistant glioma cells. The LDR and HDR radiosensitivity correlates at lower doses ( approximately 2 Gy HDR, approximately 6 Gy LDR), but not at higher doses (HDR > 4 Gy; LDR > 6 Gy). The rate of LDR-induced loss of clonogenic survival changes at approximately 24 hours; wild-type TP53 cells become more resistant and mutTP53 cells become more sensitive. Redistribution induced by LDR irradiation also changes at approximately 24 hours.
Radiosensitivity of human tumor cells to both LDR and HDR irradiation is genotype dependent. Analysis of coefficients that describe cellular radiosensitivity segregates 27 cell lines into four statistically distinct groups, each associating with specific genotypes. Changes in cellular radiosensitivity and redistribution in the cell cycle are strongly time dependent. Our data establish a genotype-dependent time-dependent model that predicts clonogenic survival, explains the inverse dose-rate effect, and suggests possible clinical applications.
我们比较了27种基因型各异的人肿瘤细胞系在低剂量率（LDR）或高剂量率（HDR）照射后的克隆形成存活率。我们测量了其中8种细胞系对LDR诱导的细胞周期再分布的敏感性。
我们测量了长达96小时的LDR（0.25 Gy/h）照射后的克隆形成存活率。我们将这些结果与HDR照射（50 Gy/h）后的克隆形成存活率进行了比较。使用流式细胞术，我们测量了其中8种细胞系在LDR照射期间LDR诱导的再分布随时间的变化。
描述LDR和HDR照射后克隆形成存活率的系数分为四个放射敏感性组，这些组与细胞基因型相关：突变型（mut）ATM、野生型TP53、mutTP53以及放射抗性胶质瘤细胞中一个未鉴定的基因。LDR和HDR放射敏感性在较低剂量（约2 Gy HDR，约6 Gy LDR）时相关，但在较高剂量（HDR > 4 Gy；LDR > 6 Gy）时不相关。LDR诱导的克隆形成存活率丧失率在约24小时时发生变化；野生型TP53细胞变得更具抗性，而mutTP53细胞变得更敏感。LDR照射诱导的再分布也在约24小时时发生变化。
人肿瘤细胞对LDR和HDR照射的放射敏感性取决于基因型。对描述细胞放射敏感性的系数进行分析，可将27种细胞系分为四个统计学上不同的组，每组与特定基因型相关。细胞放射敏感性和细胞周期再分布的变化强烈依赖于时间。我们的数据建立了一个基因型依赖性时间依赖性模型，该模型可预测克隆形成存活率，解释逆剂量率效应，并提示可能的临床应用。
