The intrinsic radiosensitivity of some human tumor cells throughout their cell cycles
The intrinsic radiosensitivity of some human tumor cells throughout their cell cycles
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DOI：
10.2307/3579497
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发表时间：
1997-04-01
影响因子：
3.4
通讯作者：
Chapman, JD
中科院分区：
文献类型：
--
作者：
Biade, S;Stobbe, CC;Chapman, JD
肿瘤细胞的内在放射敏感性在异步型人群中最常被报道，尽管已知放射敏感性的细胞周期变化是显著的。对异步人肿瘤细胞存活数据的线性二次分析表明，CW系数变化很大，而β系数变化较小。异步化群体的HT-29(结肠)、OVCAR10(卵巢)和A2780(卵巢)肿瘤细胞的α系数分别为0.03、0.16和0.47GY(-1)，根β系数为0.23~0.27GY(-1)。对每个细胞系的选择程序进行了优化，分别产生了90%的有丝分裂群体，类似于HT-29，OVCAR10和A2780细胞的80%和65%的纯度。每株有丝分裂细胞在Cs-137伽马射线照射和基因组多样性校正后表现出相似和最大的辐射敏感性，α系数接近1.3Gy1。在异步化细胞中观察到的相对辐射敏感性随着细胞周期间期的进展而保持不变。所有处于早期G(1)期的细胞在有丝分裂中都表现出明显的辐射抗性，并且在G(1)/S期边界附近观察到最大的间期放射敏感性。随着细胞进入S时相，所有细胞都变得越来越耐辐射，这种影响在OVCAR10细胞中最明显，在A2780细胞中最不明显。HT-29细胞在G(2)期仍具有相对的放射抗性。观察到的这些细胞系不同的间期放射敏感性主要是由单击灭活机制决定的。这些研究清楚地证明了单击灭活在确定人类肿瘤细胞对Cs-137伽马射线的内在辐射敏感性方面的主导作用，特别是在2Gy射线和更低剂量时。(C)1997年，由辐射研究学会提供。
The intrinsic radiosensitivity of tumor cells is most frequently reported for asynchronous populations, although cell cycle variation in radiosensitivity is known to be significant. Linear-quadratic analyses of survival data for asynchronous human tumor cells show wide variations in the cw coefficient with smaller variations in the beta coefficient. HT-29 (colon), OVCAR10 (ovary) and A2780 (ovary) tumor cells with alpha coefficients of 0.03, 0.16 and 0.47 Gy(-1), respectively, and root beta coefficients of 0.23-0.27 Gy(-1) for asynchronous populations were amenable to synchronization by mitotic selection. Selection procedures were optimized for each cell line and produced mitotic populations of >90%, similar to 80% and similar to 65% purity for HT-29, OVCAR10 and A2780 cells, respectively. Mitotic cells from each line exhibited similar and maximum radiosensitivities with alpha coefficients of similar to 1.3 Gy(-1) after irradiation with Cs-137 gamma rays and after correction for genome multiplicity. Their relative radiosensitivities observed with asynchronous cells were maintained as they progressed through interphase of the cell cycle. All cells in early G(1) phase exhibited a marked radioresistance relative to their sensitivity in mitosis, and maximum interphase radiosensitivity was observed near the G(1)/S-phase boundary. All cells became increasingly radioresistant as they moved through S phase, the effect being most pronounced for OVCAR10 cells and least pronounced for A2780 cells. HT-29 cells remained relatively radioresistant in G(2) phase. The different interphase radiosensitivities observed for these cell lines were determined mainly by the single-hit inactivation mechanism. These studies clearly demonstrate the dominant role of single-hit inactivation in determining the intrinsic radiosensitivity of human tumor cells to Cs-137 gamma rays, especially at doses of 2 Gy and less. (C) 1997 by Radiation Research Society.