Placental transport and embryonic utilization of essential metabolites in the rat at the teratogenic dose of cadmium
✍ Scribed by M. Webb; G. P. Samarawickrama
- Publisher
- John Wiley and Sons
- Year
- 1981
- Tongue
- English
- Weight
- 793 KB
- Volume
- 1
- Category
- Article
- ISSN
- 0260-437X
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✦ Synopsis
Abstract
Administration of Cd^2+^ to the 12–day pregnant rat caused a dose‐dependent inhibition of placental ^65^Zn^2+^ transport. At 4 h after the injection of the teratogenic dose (1.25 mg Cd^2+^ per kg body weight), transport of ^65^Zn^2+^ to the embryo was inhibited by 75%. This inhibition decreased with time and at 48 h was no longer statistically significant. In contrast with Zn^2+^, the administration of Cd^2+^ did not affect the transport of sugar, amino acids and nucleic acid precursors from the maternal circulation to the embryo at any time. The incorporation of [^14^C]thymidine into embryonic DNA, however, was inhibited by about 50% at 4 h and by 75% at 20 h. By 48 h it returned to control levels. Incorporation of [^14^C]formate into DNA also was reduced. Inhibition of the incorporation of L‐[^14^C]leucine into protein was apparent at 20 h, but not at 4 h, after the administration of Cd^2+^. Inhibition of DNA synthesis, which led to a significant reduction in embryonic DNA concentration at 20 h, was associated with a marked decrease in the activity in embryonic thymidine kinase. In extracts of embryos from Cd^2+^‐treated dams, the activity of this enzyme was restored to the control level by the addition of 7.7 μM zinc acetate to the assay system. In vivo, the simultaneous injection of Zn^2+^ at a 2:1 atomic ratio with Cd^2+^ prevented the inhibition of thymidine incorporation into DNA. At the teratogenic dose, only about 16 ng Cd^2+^ per g wet weight is incorporated into the embryo. The inhibition of placental transport, particularly of Zn^2+^, therefore, may be of prime importance in the teratogenic response.