Budach W, Gioioso D, Taghian A, Stuschke M, Suit H D
Department of Radiation Oncology, MGH, Boston, MA, USA.
Int J Radiat Oncol Biol Phys. 1997 Oct 1;39(3):743-50. doi: 10.1016/s0360-3016(97)00362-3.
Determination of clonogenic cell proliferation of three highly malignant squamous cell carcinomas (SCC) and two glioblastoma cell lines during a 20-day course of fractionated irradiation under in vitro conditions.
Tumor cells in exponential growth phase were plated in 24-well plastic flasks and irradiated 24 h after plating with 250 kV x-rays at room temperature. Six fractions with single doses between 0.6 and 9 Gy were administered in 1.67, 5, 10, 15, and 20 days. Colony growth was monitored for at least 60 days after completion of irradiation. Wells with confluent colonies were considered as "recurrences" and wells without colonies as "controlled." The dose required to control 50% of irradiated wells (WCD50) was estimated by a logistic regression for the different overall treatment times. The effective doubling time of clonogenic cells (T[eff]) was determined by a direct fit using the maximum likelihood method.
The increase of WCD50 within 18.3 days was highly significant for all tumor cell lines accounting for 7.9 and 12.0 Gy in the two glioblastoma cell lines and for 12.7, 14.0, and 21.7 Gy in the three SCC cell lines. The corresponding T(eff)s were 4.4 and 2.0 days for glioblastoma cell lines and 2.4, 4.2, and 1.8 days for SCC cell lines. Population doubling times (PDT) of untreated tumor cells ranged from 1.0 to 1.9 days, showing no correlation with T(eff)s. T(eff) was significantly longer than PDT in three of five tumor cell lines. No significant differences were observed comparing glioblastomas and SCC. Increase of WCD50 with time did not correlate with T(eff) but with T(eff) InSF2 (surviving fraction at 2 Gy).
The intrinsic ability of SCC and glioblastoma cells to repopulate during fractionated irradiation could be demonstrated. Repopulation induced dose loss per day depends on T(eff) and intrinsic radiation sensitivity. Proliferation during treatment was decelerated compared to pretreatment PDT in the majority of cell lines. Pretreatment cell kinetics did not predict for tumor cell proliferation during treatment.
在体外条件下，测定三种高恶性鳞状细胞癌（SCC）和两种胶质母细胞瘤细胞系在20天的分次照射过程中的克隆源性细胞增殖情况。
将处于指数生长期的肿瘤细胞接种于24孔塑料培养瓶中，接种24小时后，在室温下用250 kV X射线进行照射。在第1.67、5、10、15和20天给予6次分次照射，单次剂量在0.6至9 Gy之间。照射结束后至少监测60天的集落生长情况。集落汇合的孔被视为“复发”，无集落的孔被视为“得到控制”。通过逻辑回归分析不同总治疗时间下控制50%照射孔所需的剂量（WCD50）。使用最大似然法通过直接拟合确定克隆源性细胞的有效倍增时间（T[eff]）。
在18.3天内，所有肿瘤细胞系的WCD50增加均非常显著，两种胶质母细胞瘤细胞系分别为7.9和12.0 Gy，三种SCC细胞系分别为12.7、14.0和21.7 Gy。胶质母细胞瘤细胞系对应的T(eff)分别为4.4天和2.0天，SCC细胞系对应的T(eff)分别为2.4天、4.2天和1.8天。未处理肿瘤细胞的群体倍增时间（PDT）在1.0至1.9天之间，与T(eff)无相关性。在五个肿瘤细胞系中的三个中，T(eff)明显长于PDT。比较胶质母细胞瘤和SCC未观察到显著差异。WCD50随时间的增加与T(eff)无关，但与T(eff) InSF2（2 Gy时的存活分数）有关。
可以证明SCC和胶质母细胞瘤细胞在分次照射期间重新增殖的内在能力。每天因重新增殖导致的剂量损失取决于T(eff)和内在放射敏感性。与预处理PDT相比，大多数细胞系在治疗期间的增殖速度减慢。预处理细胞动力学不能预测治疗期间的肿瘤细胞增殖情况。
