実験的脳腫瘍に対するニトロソウレア系制癌剤ACNUと放射線の併用効果—in vitroおよびin vivoにおける細胞増殖抑制効果の検討

THE ANTI-TUMOR EFFECT OF ACNU AND X-IRRADIATION ON MOUSE GLIOMA

1．はじめに

　脳腫瘍とくに神経膠芽腫に対する治療は，外科的治療のみでは完治することは稀であり，治療成績を向上さすためには放射線療法，化学療法，免疫療法などの補助療法に期待するところが大きい．脳腫瘍に刻する手術手技がほぼ完成された現在ではこれら補助療法に関する研究の重要性が，ますます高まつている。免疫療法がいまだ確立されていない現状では，とりわけ放射線治療と化学療法のになう役割は大きい。脳腫瘍に対する化学療法については，近年ニトロソウレア系制癌剤（BCNU,CC—NU,methyl-CCNU）が注目されている。同剤は低分子，低イオン化，高脂溶性の特徴をもち，血液脳関門を通過しやすく，それ自身がもつ強い抗腫瘍性とあいまつて，臨床的・実験的脳腫瘍に対して有効であつたとの報告が最近多数なされてきた^{2,4,6,11,5,16,20,22,24）}。私達も本邦で開発されたニトロソウレア系制癌剤ACNU〔1—（4—amino−2—methyl−5—pyrimidinyl） methyl−3—（2—chloroethyl）—3—nitrosourea hydrochloride〕の抗腫瘍効果を実験的脳腫瘍モデルを用いてin vitro,in vivoで検討し，その効果を明らかにするとともに^9），臨床的知見についもすでに報告した^7）。今回，ACNUと放射線の併用効果について実験的脳腫瘍モデルを用い，とくに細胞周期解析の面から検討を加えたので報告する。

Anti-tumor activities of ACNU and X-irradiation on methylcholanthrene induced glioma in C₅₇BL mice were studied in vitro and in vivo.

In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments.

As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and X-irradiation in M phase.

As to the combined therapy of ACNU and X-irradiation, the anti-tumor effect was most remark-able when the cells were treated by X-irradiation in the G₂, M phase, which were hervested by ad-dition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and X-irradiation on the cells in G₁ phase was not so remarkable.

In vivo experiments the anti-tumor effect of ACNU and X-irradiation on subcutaneously or in-tracranially transplanted glioma in mice was inves-tigated.

Either ACNU 10 mg/kg or local X-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice.

The combination therapy was more effective than ACNU or X-irradiation alone, particularly combi-nation therapy of ACNU and repeated small doses irradiation of X-ray was remarkably effective.

Evidence obtained indicates that the combination therapy of ACNU and X-irradiation have synner-gistic anti-tumor effect on experimental mouse glioma.