ABSTRACT We examined whether vanillin (VA) and CoC'l2-6H20(CoC12), anti-mutagens, which have mutation suppressing effect, i.e., promotion of cellular repair function in vitro, can modify the teratogenicity in mice caused by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting monofunctional alkylating agent. ICR mice were treated with MNNG alone (single IP dose of 40 or 60 mg/kg) or in combination with the antimutagen on day 11 of gestation. Embryotoxicity and teratogenicity were examined at term. The incidence of MNNG-induced syndactyly in the fore- and hindlimbs was significantly decreased by VA (50 mg/kg, IP) or CoC12 (IO mg/kg, IV) and a tendency to decrease in the incidence of oligodactyly was noted as well. On the other hand, the incidence of MNNG-induced brachydactyly was increased by VA or CoC12• Though the mechanism of the modifying effects of both VA and CoC'l2 on MNNG-induced malformations could not be delineated in the present study, the results indicate that the antimutagens which stimulate DNA recombination repair in vitro modify the manifestation of malformations caused by teratogens that attack the fetal DNA in the initial teratogenic mechanism.
ABSTRACT Report of a female fetus aborted at the 25th week of gestation, with severe microcephalus, trigonocephaly, median cleft lip and palate, arhinia, and anophthalmia. On opening of the skull the cranial cavity seemed to be occupied only by hindbrain structures. The forebrain, including the tentorium cerebelli and the falx were absent. However, in the light microscope membraneous remnants of a collapsed forebrain vesicle were found. They were connected with the mid-brain bud and appeared as glio-mesenchymal membranes with an cpendymal out-line at their inner surface. There was no cranioschisis. The formal relationship of this forebrain malformation to abobar dorsal sac holoprosencephaly, and its separation from hydranencephaly are discussed. In view of the gross absence of the telencephalon and the microscopic demonstration of remnants of a proscnccphalic vesicle it is suggested to term this <missing link< in the classification of human CNS malformations pseudoaprosencephaly.
ABSTRACT A considerable number of postnatally-viable microphthalmic off-spring with optic nerves completely absent were obtained by X-irradiation at a dose of 100 R in pregnant rats on gestational day 10.5. Thirteen of 15 mi-crophthalmic eyes examined displayed histological features characteristic of aplasia of the optic nerve: complete absence of optic papilla, nerve fiber layer and retinal blood vessels, and great reduction in the number of ganglion cells. The remaining 2 eyes showed the histological features of hypoplasia of the optic nerve. The present experimental system may afford suitable materials for postnatal pathogenetic studies and also for various physiological and behavioral studies of aplasia of the optic nerve.