V. Drugs and chemical substances 1) Thalidomide 2) Actinomycin D 3) Streptonigrin 4) Chlorambucil 5) Dextroamphetamine 6) Urethane and hydroxyurea 7) Aflatoxin B_1 8) Purine analogues 9) Methyl salicylate 10) Beta-amino- 11) Trypan blue 12) Others propionitril (BAPN) VI. Zinc deficiency and cadmium VII. Tissue antiserum VIII. Hormone The problems concerning the abnormal development of the heart were discussed and summarized according to the following items: 1. The role of the genome during cardiogenesis in the embryo 2. The patterns of cardiovascular anomalies produced by different agents 3. The relationship between embryonic stage at which agents are administered and frequency of heart anomalies manifested 4. Morphology of the abnormal cardiogenesis in early stages of embryos 5. The relationship between anomalies and chromosome changes in the embryo treated with various agents 6. The relationship between anomalies and lysosome formation in embryonic cells 7. The relationship between anomalies and LDH-isozyme differentiation in early states of embryos

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著者は,クローズドコロニーとして約20年間維持されてきた日本白色種ウサギ(jw/NIBS)を用い,妊娠8日ないし15日のいずれかの妊娠日,ビタミンA30万単位(IU)/kgを1回腹腔内は注射し,その胎仔をおよぼす影響について実験を行ない,つぎの結果を得た.1)8日胎令群では,すべての胚が死亡し,可検胎仔はえられなかった.9〜15日胎令群の胎仔には,種々の外形および骨格異常,さらに発育障害が種々の頻度で成立した.2)外形および骨格異常は9〜11日胎令群の胎仔では高率に出現したが,処理時の胎令が進むとともに成立頻度は減少した.3)ウサギにおけるビタミンA過剰投与実験において,先人が記載しているように,頭蓋および顔面異常,口蓋裂,露舌,眼瞼開放,短尾,内反手,内反足,欠指,合指および合趾がみとめられた.さらに,本研究では耳介の異常,短肢,短指および短趾が低率に観察された.4)骨格系の観察により,早期胎令群の胎仔にみられた頭蓋異常は頭蓋骨の減形成によるものであるが,他方後期胎令群の胎仔にみられたそれらは前頭骨および頭頂骨の癒合あるいは隆起にもとづくものであろう.このように頭蓋骨に発現した異常は,ビタミンAの処理をうけた発生段階により,それらの形態発生機序を異にするようにみられた.5)他の特徴的な異常のうち,顔面異常は鼻骨,上顎骨,切歯骨および下顎骨の形成不全に,短肢は上腕骨および前腕骨の短縮,肥厚および癒合に,欠指,短指および短趾は指骨の全あるいは部分欠損にもとづいて発現するものであろう.本研究について終始御指導,御校閲を賜わった恩師,田島正典博士,ならびに武田薬品株式会社生物研究所梶原彊博士に深甚の謝意を表する.また,本研究の機会を与えられた日本生物科学研究所所長中村〓治博士に深謝する.さらに,実験に協力していただいた井上洋子嬢に感謝する.

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Wister rats were treated with a single intraperitoneal injection of 0.2mg/kg of vincristine of day 8 of pregnancy, and the fatuses were examined externally on day 20. Major malformations were as follows: Anophthalmos and microphthaomos were 44.10%, malformations of the CNS were 45.13%, and those of the face were 48.21%. On malformations of the eye, bilateral cases were 66.28% and unilateral ones were 33. 72%. Malformed eyes on the right side were 47.55%, and those on the left side were 52.45%. Incidence of anophthalmos was 53.85%, that of microphthalmos was 45.45%. Besides, there were open eyelids, 6.29%. When they were examined histologically, almost all cases grossly diagnosed as anophthalmos were proved to be microphthalmos which had some components of the eye cup. Under a microscope, there were found few complete anophthalmos, many microphthalmoses of extreme degree, "some with complicated retinal foldings, few with slight coloboma of the retina, etc. Another series of experiments were dynamic studies of the abnormal morphogenesis of the eye. Embryos were examined on day 10, i. e. , two days after the treatment; thereafter they were taken out every 24 hours until day 19. These were examined histologically. A11 cases examined on day 10 had the eye vesicle. Even those with intense cranioschisis also had the eye vesicle. However, on day 11 when the eye vesicle develops into the eye cup, the process of the development was arrested or involved in an abnormal condition. When embryos were examined on day 12, the eye cup was small in size suggesting sequential microphthalmos. Of those examined of day 13, there were cases suggesting initial involvement which would lead to anophthalmos. In such cases, only rudiments of the eye cup were detected. On the later stages of the development, i. E., after day 13, besides cases of the above mentioned abnormal conditions, absence of the optic nerve and sometimes malformations of the diencephalon were associated. In the above results, a spectrum of malformations of the eye was observed such as from a complete anophthalmos to a slight coloboma of the retina. However, these malformations of the eye induced by vincristine were generally similar to those produced by other extrinsic factors. All cases of anophthalmoses were degenerative anophthalmoses, and no cases of primary anoththalmos were found.

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