グリオーマ細胞とDibutyryl cyclic AMP—その細胞動態に及ぼす影響

CELL KINETIC CHANGES OF MALIGNANT GLIOMA CELLS TREATED WITH DBCAMP

I．はじめに

　Dibutryl cyclic adenosine monophosphate （DBcAMPと略記）が悪性グリオーマの培養細胞に作用して形態学的に良性化ないしは分化の方向へ変化させるという現象は1971年永井^25）等の報告以来本邦でも何回か発表されて来ている^{19,20,23,24）}。著者等は同物質がin vivoでもC57BLマウスに移植した203GL glioblastomaに対して49.2％の生長抑制のあることを認め^29,32），さらに動物実験によりこの物質を静注，髄液注の方法で投与した場合，一過性の血糖上昇や血圧の上昇は認めるが特に著るしい副作用は認めていないことを確かめた^28）。これらの結果はLevineの報告例^10,11）と一致するものである。こうして最近はこの物質の増殖抑制およびcell differen—tiatorとしての効果が注目され従来の放射線，免疫，化学療法とは異なる作用機序による新しい脳腫瘍治療剤として考えられ始めて来た^{12,13,14,21,28）}。この時点においてDBcAMPが悪性腫瘍細胞の細胞動態にいかなる影響を与えているかを知ることは，この物質を臨床に応用する場合，その投与法，期間，投与量等を決定するにきわめて重要なことであると考えられる^30,31）。

　本論文においてはAutoradiographyを用いておこなつた悪性グリオーマ培養細胞の生長解析について

The effect of dibutyryl cyclic AMP (DBcAMP)on malignant glioma cells was studied in vivo andin vitro.

1) The malignant glioma cells in culture showedbenign transformation; and

2) Their growth was suppressed by adminis-tration of 1-3 mM DBcAMP. The effect of DBcAMPon the cell kinetics of the malignant gliomas wasreported. The labeling indexes of DBcAMP treat-ed cells which were measured by a pulse labelingof tritiated thymidine were reduced by 36. 2-65.0%,compared with those of controls. It was observedthat the cells having the higher labeling indexesin control showed the more remarkable decreaseof the labeling indexes.

The alteration of growth fraction by DBcAMPwas measured by continuous administration of tri-tiated thymidine for 30 hours. The result revealedthat the growth fraction was decreased by 50-60%in the treated groups. The change in the durationof S phase was examined by double autoradiographymethod and 40-60% increase of the duration of Sphase was noticed in DBcAMP treated groups.DBcAMP has a remarkable effect in facilitatingthe transition from the proliferating cells into non-proliferating pool, as well as the prolongation ofS phase. It was suggested that the DBcAMP actedon the cell growth as a regulating factor. Thegrowth inhibitory effect depended not only on theconcentration of DBcAMP, but also on the durationof the treatment with this substance. Its effectsreached the maximum level at the concentrationmore than 1 mM of DBcAMP while the incubationtook over 12 hours. DBcAMP, may offer an entirelynew approach for the treatment of malignantgliomas, by combination with radio-, immuno-, orchemotherapy in the near future.