脳腫瘍の化学療法に対するflow cytometry分析の応用—第1報 各種抗癌剤による細胞動態の変化

APPLICATION OF FLOW CYTOMETRIC ANALYSIS TO BRAIN TUMOR CHEMOTHERAPY. : REPORT 1 : CHANGES OF CELL KINETICS INDUCED BY ANTICANCER DRUGS

はじめに

　脳腫瘍の化学療法，あるいは化学療法と放射線療法の併用によつて効果的に治療を行なおうとする場合，細胞増殖の動態を把握して，それによつて治療計画を立てていくことが重要視されている。最近はflow cytometry法により，短時間にそれのDNA分布を分析できることから，化学療法後の細胞のperturbationを知ることにより，より効果的な方法を見つけようという努力がなされている。しかしながらある一定の濃度においてのみの結果からperturbationの強弱を論じ，それによつて臨床に応用することは非常に危険が大きい。すなわち用いるべき薬剤の特徴—低濃度でperturbationをおこすのか，高濃度でひきおこすのかなど—を臨床につかわれる濃度を中心に検討が必要であるからである。脳腫瘍細胞を用いてのこれらの検討はまだ部分的にしか報告をみない。そこで各種抗癌剤の細胞動態に及ぼす影響につき，化学療法への応用という観点から研究した。

It has been reported that flow cytometric analy-sis offers good indicators to select drugs for chemo-therapy of malignant neoplasms, however, there are still few reports to try to apply these data to clinical treatment. For this purpose perturbation of cell cycle traverse which induced by several anticancer drugs was studied to determined the fun-damental factors to indicate the sensitivity of each drugs.

Results were :

1) Drugs showed high efficiency of accumulation of cells in SG₂M phase even in low concentra- tion ; MMC, AD, CQ.

2) Drugs showed high efficiency of accumulation of cells in SG₂M from low concentration to high concentration ; Vincristine.

3) Drugs which showed accumulation of SG₂M in high concentration ; ACNU, BCNU.

9L rat glioma cells treated with BCNU showed high efficiency of acumulation of cells in SG₂M phase. In this cell line cytocidal effect was high. However, C₆ cells which showed low accumulation in SG₂M even by treatment with high concentration of BCNU revealed quite resistant to anticancer drugs from nitrosourea derivatives (ACNU, BCNU). Cytocidal effect of MMC and ACNU on C₆ glioma cells was studied by colony foming efficiency assay using multicell spheroids treated with these drugs and it was discussed the correlation between percent of accumulated cells and cytocidal effect of each drug.