title: Effects of Taxol plus radiation on the apoptotic and mitotic indices of mouse intestinal crypt cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiation Oncology, Uludag University Medical College, Bursa, Turkey. lutfi@uludag.edu.tr
authors.forename: L
authors.initials: L
authors.lastname: Ozkan
authors.forename: S
authors.initials: S
authors.lastname: Ozuysal
authors.forename: U
authors.initials: U
authors.lastname: Egeli
authors.forename: S B
authors.initials: SB
authors.lastname: Adim
authors.forename: B
authors.initials: B
authors.lastname: Tunca
authors.forename: N
authors.initials: N
authors.lastname: Aydemir
authors.forename: G
authors.initials: G
authors.lastname: Ceçener
authors.forename: E
authors.initials: E
authors.lastname: Ergül
authors.forename: G
authors.initials: G
authors.lastname: Akpinar
authors.forename: C
authors.initials: C
authors.lastname: Cimen
authors.forename: K
authors.initials: K
authors.lastname: Engin
authors.forename: M M
authors.initials: MM
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D017024:Chemotherapy, Adjuvant; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D051379:Mice; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D008940:Mitotic Index; D017239:Paclitaxel / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D018714:Radiotherapy, Adjuvant
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel