Radioautographic study of RNA synthesis in normal and actinomycin D treated rat embryos

Incorporation of tritiated uridine in embryonic and extraembryonic tissues of normal and actinomycin D treated rats was determined by radioautography on days 7 through 11 of gestation. Precursor incorporation was equated with RNA synthesis and correlated with developmental events and with previously determined teratogenic effects of actinomycin D. Uptake of uridine increased progressively in untreated animals from days 7 through 10 in decidua, trophoblastic giant cells, and visceral and parietal yolk sac endoderm, and remained relatively high in all except visceral yolk endoderm which dropped sharply on day 11. Actinomycin D did not significantly alter uptake in decidua and parietal yolk sac endoderm but caused appreciable reduction of uptake in trophoblast and visceral yolk sac epithelium on days 9 and 10. Uridine incorporation in embryonic ectoderm of untreated animals was relatively low but measurable at all times after day 7 and increased steadily through day 11. It was significantly depressed by actinomycin D on days 9 and 10. These observations correlated well with known developmental events and with teratogenic manifestations following actinomycin D treatment. Tritiated actinomycin D was shown by radioautography to be present in the embryo on day 9, 10 and 11 of gestation, and was shown to be bound to DNA, by virtue of its disappearance after application of deoxyribonuclease. It was concluded that the teratogenic action of actinomycin D in rats is probably dependent on direct intraembryonic inhibition of RNA synthesis.