脳腫瘍の phase-synchronization に関する基礎的研究 : -II 各種制癌剤および物理的要因に基づく細胞周期の変動-

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Perturbed cellular kinetics of experimental C_6 brain tumor under the effect of chemotherapeutic agents and physical condition was investigated for establishing the optimal regime of brain tumor synchronization as pretreatment for radiotherapy. Cultured C_6 strain was treated for 72 hours with Vincristine, Vinblastine, ACNU, BCNU,5-FU, Methotraxate, Bleomycin, hyperthemia or microwave irradiation. The cell cycle distribution was analysed by the histograms of pulse-cytophotometry with DNA specific fluorescent stain of ethidium bromide in cell suspension. The quantitative evaluation of cell cycle phase was obtained using a computerized mathematical model.Potent synchronization in the G_2-M phase was observed in the group treated with Vincristine, Vinblastine, ACNU and BCNU. In the Vincristine and ACNU-treated group, G_2-M phase accumulation increased gradually during 72 hrs. Maximtum level of G_2-M phase was 47.6% of diploid cell population by 72 hrs-contact with Vincristine, and 47.2% by ACNU (control 10%). In the Vinblastine and BCNU-treated group, G_2-M phase-accumulation increased rapidly during 24 hrs. and then the accumulated cells in G_2-M phase became dead within 72 hrs. Hyperthemia (40°) accumulated 37% of total cells into the G_2-M phase. In other treatments, the cells in G_2-M phase were below 30% of total cells. Significant synchronization depends on concentration, exposure time and tumor specificity of agents, even in vitro system.The effect of combined use of ACNU and Vincristine was investigated in vivo in intracerebrally innoculated C_6 tumor. A relatively low amount of proliferating fraction was shown in comparison with cultured C_6 glioma. After the 9th day from innoculation, combined administration of Vincristine, 0.025 mg/kg on 3 successive days, and ACNU, 0.8 mg/kg, on 2 successive days from the second day of Vincristine was intravenously performed via femoral vein of rats. The administration of Vincristine 0.25mg/kg and ACNU 0.8 mg/kg was also tried in the same regimen in another group of rats. The cells in G_2-M phase increased to 21% in lower concentration and 29% of total cells in higher concentration (control 6%). These results showed the possibility of the choice of vinca alkaloids and nitrosourea derivatives for cellular synchronization as pretreatment for radiotherapy.
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脳腫瘍の phase-synchronization に関する基礎的研究 : -II 各種制癌剤および物理的要因に基づく細胞周期の変動-

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