Chromosome changes in embryos treated with various teratogens.

The association of chromosome changes with certain syndromes of congenital malformations has raised new questions as to the possible role of abnormal chromosome complements in teratogenesis. For example, mosaics are thought to originate in the first divisions of the fertilized ovum, and one may ask how late in embryogenesis permanent chromosome changes can be induced. Investigations have been undertaken in this laboratory to ascertain whether teratogens administered to pregnant rats on the 11-13th days of gestation, when many malformations can be induced, will result in embryos with chromosomal aberrations as well as malformations. In a previous report (Soukup, Takacs & Warkany, 1965) we have described experiments in which pregnant rats were treated with teratogenic doses of X-ray followed by examination of embryos for detectable chromosome abnormalities. In embryos irradiated on the 13th day with 400 r and examined 6-12 h later, approximately 60 % of the countable metaphase figures revealed chromosome aberrations. Detectable chromosome damage dropped sharply within 24 h after irradiation, and by 72 h it approached control levels. It was concluded that chromosome aberrations induced by X-rays during organogenesis disappeared rapidly and almost completely even in grossly abnormal embryos. When the X-ray dose was reduced to 200 r, which is still a teratogenic dose, only 7 % abnormal metaphase figures were observed 6 h after irradiation. In the present investigation results obtained from embryos exposed to some teratogens other than X-rays are reported. The known chemical teratogens, nitrogen mustard, chlorambucil, streptonigrin and hydroxyurea, were injected into pregnant rats; thalidomide was fed to pregnant rabbits. In addition, embryos from rats exposed to a teratogenic riboflavin-deficient diet were examined for chromosome changes. 1 Authors' address: Children's Hospital Research Foundation, Elland Avenue and Bethesda, Cincinnati, Ohio 45229, U.S.A.