Effects of Taxol plus radiation on the apoptotic and mitotic indices of mouse intestinal crypt cells

• Published in: Journal of cancer research and clinical oncology 2001-07, Vol.127 (7), p.433-438
• Main Authors: OZKAN, L, OZUYSAL, S, ENGIN, K, AHMED, M. M, EGELI, Ü, ADIM, S. B, TUNCA, B, AYDEMIR, N, CECENER, G, ERGÜL, E, AKPINAR, G, CIMEN, C
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Apoptosis - radiation effects; Biological and medical sciences; Chemotherapy, Adjuvant; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Intestinal Mucosa - drug effects; Intestinal Mucosa - radiation effects; Intestinal Mucosa - ultrastructure; Medical sciences; Mice; Mitosis - drug effects; Mitosis - radiation effects; Mitotic Index; Paclitaxel - pharmacology; Pharmacology. Drug treatments; Radiation-Sensitizing Agents - pharmacology; Radiotherapy, Adjuvant
• ISSN: 0171-5216; 1432-1335
• 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.