Ethylnitrosoureaによる胎生期脳障害の早期変化について

INITIAL CELLULAR DAMAGE IN THE DEVELOPING RAT BRAIN CAUSED BY CYTOTOXICITY OF ETHYLNITROSOUREA

　抄録　化学発癌物質であると同時に，細胞毒としても働くethylnitrosourea （ENU）を発生途上のラットに投与し，大脳皮質の細胞障害の初期変化を形態学的に明らかにすることを目的とした。Neuroblastを形成し始めて間もない時期に当る妊娠16日目のラットにENUを投与し，初めの24時間は1時間毎の，以後は24時間毎の胎仔を，出生後は3日目までの新生仔を，それぞれ経心的灌流固定後、光顕および電顕下に観察した。ENU投与後，matrix cell layerのS期に組当する部にある細胞の核に最初の変性が認められ，やがてmatrix cell layer全体に変性細胞核が散見され，分裂中のmatrix cellにも認められた。時間の経過と共に，neuroblastと思われる細胞の変性はmigrating zoneの中にも出現し始め，最初にmatrix cell layerに核変化が発現した後約3時間で皮質層直下のneuroblastにまで変性像は広く散見されるに至った。他方，投与時すでに形成されていたcortical plateはそのまま残存していた。以上の所見からENUによる神経系の選択的な障害は，S期以後の分裂期に入るmatrix cellと，それより形成されたばかりのneuroblastに発現することを認めた。

Initial cellular degeneration in developing rat fetal brains were induced during the early cytogenetic period of neuroblasts by cytotoxic action of ethylnitrosourea (ENU). This was trans-placentally administered.

After a single intravenous administration of 60 mg/kg body weight ENU to 16 th day-pregnant rats, each fetus was removed surgically from theuteri every hour for 24 hours and every day for 9 days. These were fixed by the transcardial perfusion method to observe them with light and electron microscopes.

From 4 hours after the ENU-treatment, the degenerative alteration of cells, characterized ultrastructurally by cytoplasmic condensation and nuclear pyknosis, developed selectively in the matrix cell layer of the fetal cerebrum where active cell division was carried out to produce neuroblasts. Cellular degeneration was first noticed at the zone of DNA synthesis and then all the matrix cell layer including the mitotic phase. Furthermore, the cell processes of matrix cells, or so-called radial fibers, were also recognized to be in the same degenerative processes.

These affected cells increased in number and became arranged in columns along the radial fibers through the process of time, and successively migrated to the migrating zone through the outer part of the matrix cell layer.At 10 hours after treatment, many cells were observed in the migrating zone and a few cells were noticed in the matrix cell layer. The degenerated neuroblasts reached the cortical plate about 3 hours after the development of initial degeneration.

In contrast, the neuroblasts in the cerebral cortical plate which had already been formed at the time of ENU administration were not affected by the ENU and persisted for the following develop-ment.

Similarly, the midbrain and cerebellum showed only a few degenerative changes in their matrix cell layers.

From these findings it was suggested that cellular damage caused by ENU occurred select-ively in the actively proliferating matrix cells at the generating cycle stage from the S-to M phase, and in newly formed neuroblasts.