Ozkan L, Ozuysal S, Egeli U, Adim S B, Tunca B, Aydemir N, Ceçener G, Ergül E, Akpinar G, Cimen C, Engin K, Ahmed M M
Department of Radiation Oncology, Uludag University Medical College, Bursa, Turkey.
J Cancer Res Clin Oncol. 2001 Jul;127(7):433-8. doi: 10.1007/s004320100240.
In this study we investigated the effect of Taxol, radiation, or Taxol plus radiation on highly proliferative normal tissue--the intestinal crypt cells of Swiss albino mice.
Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered by bolus intravenously through the tail vein. Radiation was given using a linear accelerator. There were four treatment categories, which comprised a total of 34 groups. Each group consisted of five animals. The first category was a control category which comprised one group (n = 5). The second treatment category was Taxol alone which comprised three groups (n = 15). The third treatment category was radiation alone which comprised three groups (n = 15). The fourth treatment category was Taxol plus radiation which comprised 27 groups (n = 135). Mice were killed 24 h after Taxol or radiation or combined administration using ether anesthesia. Using a light microscope, apoptotic and mitotic indices were counted on jejunal crypt cells of mice that were stained with hematoxylin-eosin. Differences between groups were statistically evaluated with Student's t-test.
Taxol caused a dose-dependent increase in apoptosis (P = 0.045) and decreased the mitotic index (P = 0.006) at high doses. Similarly, radiation caused a dose-dependent increase in apoptosis (P = 0.046) and decreased the mitotic index (P = 0.299) at higher radiation doses. Compared to radiation alone, Taxol caused a significant induction of apoptosis (P = 0.010). In combination, no significant radiosensitizing effect of Taxol was observed (enhancement ratio < 1), when compared to radiation alone. However, an increase in apoptosis was observed after 24 h of Taxol exposure when compared to 12 or 48 h of Taxol exposure (P = 0.0001 and P = 0.0001).
These findings suggest that Taxol did not cause a radiosensitizing effect in intestinal crypt cells. However, a 24-hour pretreatment of Taxol exposure followed by radiation caused significant induction of apoptosis and reduction of the mitotic index when compared to other Taxol timing sequences. Thus, the lack of a radiosensitizing effect of Taxol in these proliferative cells may be due to enhanced mitotic death rather than apoptotic death.
在本研究中，我们调查了紫杉醇、辐射或紫杉醇联合辐射对高度增殖的正常组织——瑞士白化小鼠肠隐窝细胞的影响。
本研究使用3 - 4月龄的瑞士白化小鼠。紫杉醇通过尾静脉大剂量静脉注射给药。使用直线加速器进行辐射。有四个治疗类别，共包括34组。每组由五只动物组成。第一类是对照组，包括一组（n = 5）。第二类治疗是单独使用紫杉醇，包括三组（n = 15）。第三类治疗是单独辐射，包括三组（n = 15）。第四类治疗是紫杉醇联合辐射，包括27组（n = 135）。在紫杉醇、辐射或联合给药后24小时，使用乙醚麻醉处死小鼠。使用光学显微镜，对用苏木精 - 伊红染色的小鼠空肠隐窝细胞计数凋亡指数和有丝分裂指数。组间差异用学生t检验进行统计学评估。
紫杉醇导致凋亡呈剂量依赖性增加（P = 0.045），并在高剂量时降低有丝分裂指数（P = 0.006）。同样，辐射在较高辐射剂量下导致凋亡呈剂量依赖性增加（P = 0.046），并降低有丝分裂指数（P = 0.299）。与单独辐射相比，紫杉醇显著诱导凋亡（P = 0.010）。联合使用时，与单独辐射相比，未观察到紫杉醇有显著的放射增敏作用（增强比 < 1）。然而，与紫杉醇暴露12小时或48小时相比，紫杉醇暴露24小时后观察到凋亡增加（P = 0.0001和P = 0.0001）。
这些发现表明，紫杉醇在肠隐窝细胞中未产生放射增敏作用。然而，与其他紫杉醇给药时间序列相比，紫杉醇暴露24小时后再进行辐射导致显著的凋亡诱导和有丝分裂指数降低。因此，紫杉醇在这些增殖细胞中缺乏放射增敏作用可能是由于有丝分裂死亡增强而非凋亡死亡。
