Summary
In order to elucidate the phase specificity of the embryo-lethal and teratogenic action of actinomycin D (day 5–10 of gestation) rats received 3H-actinomycin D at different times of gestation. The distribution of the radioactivity in the fetus and the placenta was measured. Moreover, the effects of actinomycin D on the RNA polymerase reactions in isolated nuclei of the decidual and fetal tissue were studied. The biochemical results were correlated electron microscopically with specific alterations occurring in different structures of the total implantation sites.
These studies show that the time-dependent embryo-lethal and teratogenic effects of actinomycin D result from a lesion of the embryo and the decidua. The effects of the decidua occur at an earlier time and are more pronounced as compared to those of the embryo. Since the decidua is significant for the nutrition of the embryo till closure of the yolk-sac and beginning of the yolk-sac circulation (day 10 of gestation), the direct effects of actinomycin D on the embryo are intensified by the lesion of the decidua. After day 10 of gestation till the beginning of the placental function 3H-actinomycin D passes over to the embryo. But the concentration-even after a dose of 1 mg/kg-does not suffice to inhibit in vivo RNA polymerase reactions in isolated nuclei.
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Köhler, E., Merker, H.J. Studies on the teratogenic phase specificity of actinomycin D in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 31–44 (1972). https://doi.org/10.1007/BF00505066
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DOI: https://doi.org/10.1007/BF00505066