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Placental transport and embryonic utilization of essential metabolites in the rat at the teratogenic dose of cadmium
Author(s) -
Webb M.,
Samarawickrama G. P.
Publication year - 1981
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550010507
Subject(s) - teratology , chemistry , embryo , dna synthesis , thymidine , biochemistry , nucleic acid , in vivo , biology , dna , endocrinology , fetus , pregnancy , microbiology and biotechnology , genetics
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.