The in vivo biosynthesis of DNA, RNA, and proteins by mouse embryos after a teratogenic dose of cyclophosphamide.

Abstract

AbstractPregnant Swiss‐Webster mice received 20 mg/kg cyclophosphamide ip on day 11 of gestation and 100–125 μCi/kg 14C‐labeled thymidine, orotic acid, uridine, or leucine at various times afterwards. DNA synthesis in embryos, as measured by 14C‐thymidine incorporation, was significantly reduced at 12 h but not 3, 6, 24, 48, or 72 h after treatment, and embryonic DNA was reduced at 12, 24, 48, and 72 h. 14C‐thymidine incorporation and DNA content were also reduced in placentas and maternal livers after a delay of at least 6 h. Embryonic protein synthesis, as measured by 14C‐leucine incorporation, was significantly reduced at 72 and 96 h after treatment. Embryonic RNA synthesis or content was not significantly affected. It was concluded that a teratogenic dose of cyclophosphamide quantitatively affects the synthesis of DNA and protein in the mouse embryo. The temporal aspects of the changes indicated that the effects on DNA synthesis may be the cause of induced developmental defects but effects on protein synthesis appear to be the result rather than the cause of the defects.