Cytosine Arabinoside投与による小脳外顆粒細胞傷害に関する電顕的研究

EFFECT OF CYTOSINE ARABINOSIDE ON EXTERNAL GRANULAR LAYER OF SUCKLING MOUSE CEREBELLUM AN ELECTRONMICROSCOPIC STUDY

I．はじめに

　小脳の小型ニューロンである顆粒細胞，星状細胞（Sa—tellate cell），籠細胞（basket cell）などは，動物の種を問わずそのほとんどが小脳外顆粒層において出生後に産生されることは周知のところである^{2,9,10,23,29）}。また，これらのニューロン産生が活発な新生仔，乳仔期にある種の化学物質^{5,25,30,31,39）}，放射線照射，^1,13），ある種のウイルス感染などがあると^15,24），外顆粒層の増殖中の細胞が壊死に陥り，のちに小脳の低形成，細胞構築異常が惹起されることはすでに諸家の報告しているところである。

　ところで，化学物質の投与，あるいは放射線照射に起因するこれら小脳形成障筈の発生病理に関しては，これまでの報告のほとんどが光顕レベルでの組織学的研究によるものである。本研究では小脳形成障害を惹起することが知られている化学物質のうち，抗腫瘍剤，抗ウイルス剤として臨床的にも使用頻度の高いcytosine arabi—noside （以下ara-cと略す。）を用い^4,8,34），小脳外顆顆層における未分化細胞（germinal cell）の壊死過程，破壊産物清掃過程を電子顕微鏡により観察した。

The external germinal cell at the external granu-lar layer in the developing cerebellum proliferates intensely during two weeks after birth. Experi-mental inhibition of DNA-synthesis of the cell, therefore, should inhibit the proliferation of ger-minal cells, thus causing cerebellar hypoplasia. The present investigation aimed at determining the effect of an inhibitor of DNA-synthesis, cytosine arabinoside (ara-C), on the external granular layer.

Three-day-old mice were injected subcutaneously with 30 mg/kg body weight of ara-C, and were killed at one hour interval after injection. Then, the external granular layers were examined by light and electron microscope. The results were as follows.

1) Up to 3 hours after injection, degenerative cells are not observed. Degenerative cells became apparent at the external granular layer at 4 hours after injection. After 4 hours, picnotic cells in-creased rapidly to become maximum at 6-9 hours after treatment. After 9 hours, picnotic cells gradu-ally decreased to disappear after 16 hours.

2) Pathological changes in the external germinal cells after ara-C treatment, were first noted as the chromatin condensation around nuclear envelope, which finally became whole nuclear condensation. A few hours later the first sign of nuclear change, various inclusion bodies appeared in the cytoplasm. These inclusion bodies were subsequently released outside the cell body.

3) Cell debris were phagocyted by two different types of cells. These cells had close similarity with the germinal cell and macrophage in many respects.