Investigation of genotoxic effect of taxol plus radiation on mice bone marrow cells.
In this study, we investigated the genotoxic effect of taxol, radiation, or taxol plus radiation on highly proliferative normal tissue-bone marrow cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered bolus intravenously through the tail vein. Radiation was given by using a linear accelerator. There were four treatment categories, which had a total of 34 groups. Each group consisted of five animals. The first was the control category that had one group (n = 5). The second treatment category was taxol alone, which had three groups as per taxol dose alone (n = 15). The third treatment category was radiation alone, which had three groups as per the radiation dose (n = 15). The fourth treatment category was taxol plus radiation, which had 27 groups as per combined radiation dose plus taxol dose concentration and as per pre-treatment timing sequence of taxol before radiation (n = 135). Mice were sacrificed 24 h after taxol or radiation or combined administration using ether anesthesia. The cells were then dropped on two labeled slides, flamed, air dried, and stained in 7% Giemsa; 20-30 well-spread mitotic metaphases were analyzed for each animal; the cells with chromosome breaks, acentric fragments, and rearrangements were evaluated on x1,000 magnification with light microscope (Zeiss axioplan). The mitotic index was determined by counting the number of mitotic cells among 1,000 cells per animal. Differences between groups were evaluated with Student's t-test statistically. Taxol caused a dose-dependent increase in chromosomal aberrations (P = 0.027). Similarly, radiation caused a dose-dependent increase in chromosomal aberrations (P = 0.003) and decreased mitotic index (P = 0.002). In combination, there were a small enhancements at the 40 mg/kg taxol dose level and at 0.25 and 0.5 Gy radiation doses in the 48 h group. However, an increase in chromosomal aberrations was observed after 48 hours of taxol exposure when compared 12 or 24 h of taxol exposure (P = 0.001 and P = 0.019). These findings suggest that taxol at the high doses with low dose radiation caused radiosensitizing effect in bone marrow cells. Forty-eight-hour pretreatment of taxol exposure followed by radiation caused significant induction of chromosomal aberrations and a reduction of mitotic index when compared to other taxol timing sequence.
Ozkan
Lütfi
L
Department of Radiation Oncology, Uludag University Medical College, Görükle, Bursa, Turkey. lutfi@uludag.edu.tr
Egeli
Unal
U
Tunca
Berrin
B
Aydemir
Nilüfer
N
Ceçener
Gülşah
G
Akpinar
Gürler
G
Ergül
Emel
E
Cimen
Ciğdem
C
Ozuysal
Sema
S
Kahraman-Cetintaş
Sibel
S
Engin
Kayihan
K
Ahmed
Mansoor M
MM
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D008940:Mitotic Index; D017239:Paclitaxel / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel