A comparison of the in vivo and in vitro response of mammalian embryos to a teratogenic insult.
This study serves to further define the capabilities of the whole embryo culture system using the known teratogen, hydroxyurea (HU). An initial in vivo study was performed whereby day 9 pregnant mothers were injected i.p. with 300 mg/kg HU. Dams were sacrificed 2 days later and embryos were analyzed for malformations and total embryonic protein. In addition, the peak plasma value from injected dams was found to be approximately 300 micrograms/ml with a plasma half-life of 30 min. These values were then reproduced in the culture system with results noted in cultured embryos with respect to the types of malformations found. Additional in vitro experiments were performed varying both exposure time and drug level concentrations. Results indicate that both of these parameters are important considerations when designing in vitro experiments.
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000818:Animals; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006207:Half-Life; D006918:Hydroxyurea / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism; D013723:Teratogens / Q000633:toxicity*
D011506:Proteins; D013723:Teratogens; D006918:Hydroxyurea