Guo M, Chen C, Vidair C, Marino S, Dewey W C, Ling C C
Medical Physics Department and Radiation Biophysics Laboratory, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
Radiat Res. 1997 Mar;147(3):295-303.
For REC:myc(ch1), Rat1 and Rat1:myc(b) cells, we determined the events in the development of radiation-induced apoptosis to be in the following order: cell division followed by chromatin condensation, membrane blebbing, loss of adhesion and the uptake of vital dye. Experimental data which were obtained using 4He ions of well-defined energies and which compared the dependence of apoptosis and clonogenic survival on 4He range strongly suggested that in our cells both apoptosis and loss of clonogenic survival resulted from radiation damage to the cell nucleus. Corroboratory evidence was that BrdU incorporation sensitized these cells to radiation-induced apoptosis. Comparing the dose response for apoptosis and the clonogenic survival curves for Rat1 and Rat1:myc(b) cells, we concluded that radiation-induced apoptosis contributed to the overall radiation-induced cell inactivation as assayed by clonogenic survival, and that a modified linear-quadratic model, proposed previously, modeled such a contribution effectively. In the same context, the selective increase in radiation-induced apoptosis during late S and G2 phases reduced the relative radioresistance observed for clonogenic survival during late S and G2 phases.
对于REC:myc(ch1)、Rat1和Rat1:myc(b)细胞,我们确定辐射诱导凋亡发生过程中的事件顺序如下:细胞分裂,随后是染色质浓缩、细胞膜起泡、失去黏附力以及摄取活性染料。使用能量明确的4He离子获得的实验数据,比较了凋亡和克隆形成存活对4He射程的依赖性,强烈表明在我们的细胞中,凋亡和克隆形成存活能力的丧失均源于细胞核受到的辐射损伤。佐证是溴脱氧尿苷(BrdU)掺入使这些细胞对辐射诱导的凋亡敏感。比较凋亡的剂量反应以及Rat1和Rat1:myc(b)细胞的克隆形成存活曲线,我们得出结论,辐射诱导的凋亡导致了通过克隆形成存活测定的总体辐射诱导细胞失活,并且先前提出的修正线性二次模型有效地模拟了这种作用。在相同背景下,S期晚期和G2期期间辐射诱导凋亡的选择性增加降低了在S期晚期和G2期期间克隆形成存活所观察到的相对放射抗性。