Warner C W, Sadler T W, Shockey J, Smith M K
Toxicology. 1983 Nov;28(4):271-82. doi: 10.1016/0300-483x(83)90001-x.
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.
本研究旨在利用已知致畸剂羟基脲(HU)进一步明确全胚胎培养系统的能力。首先进行了一项体内研究,给妊娠第9天的母鼠腹腔注射300mg/kg的HU。2天后处死母鼠,对胚胎进行畸形和总胚胎蛋白分析。此外,发现注射母鼠的血浆峰值约为300微克/毫升,血浆半衰期为30分钟。然后在培养系统中重现这些值,并记录培养胚胎中发现的畸形类型。还进行了额外的体外实验,改变暴露时间和药物浓度水平。结果表明,在设计体外实验时,这两个参数都是重要的考虑因素。