Stahlmann R, Klug S, Foerster M, Neubert D
Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Germany.
Reprod Toxicol. 1993;7 Suppl 1:129-43. doi: 10.1016/0890-6238(93)90079-m.
Culture methods have become important tools for elucidating the prenatal toxicity of drugs and other xenobiotics. In this paper we will review how we used in vitro as well as in vivo approaches to demonstrate the teratogenic potential of aciclovir and other related virustatic agents. In addition, some new data on this topic will be given. The teratogenic potential of the virustatic agent aciclovir was not recognized in routinely performed segment-II-studies, but the first indication came from experiments with the culture of rat embryos. Subsequently, the findings were confirmed in modified in vivo tests and it became clear that out of a group of six related drugs aciclovir exhibited the highest potential for prenatal toxicity. The effects of aciclovir on limb development were not pronounced--this has been shown with in vitro and in vivo experiments as well. In vivo experiments first indicated that the prenatal development of the thymus is disturbed by aciclovir. This effect was further studied with the culture of fetal thymuses and again the effect of aciclovir could be compared with related drugs. In summary, our work with virustatics during the last years has shown that in vivo and in vitro approaches are by no means competitive and that a combination of both approaches can provide a solid basis for a toxicologic evaluation.
培养方法已成为阐明药物和其他外源性物质产前毒性的重要工具。在本文中，我们将回顾我们如何使用体外和体内方法来证明阿昔洛韦及其他相关抗病毒药物的致畸潜力。此外，还将给出关于该主题的一些新数据。在常规进行的第二阶段研究中，抗病毒药物阿昔洛韦的致畸潜力未被识别，但首个迹象来自大鼠胚胎培养实验。随后，这些发现在改良的体内试验中得到证实，并且很明显，在一组六种相关药物中，阿昔洛韦表现出最高的产前毒性潜力。阿昔洛韦对肢体发育的影响并不显著——这在体外和体内实验中均已得到证实。体内实验首先表明，阿昔洛韦会干扰胸腺的产前发育。通过胎儿胸腺培养对这一效应进行了进一步研究，并且再次将阿昔洛韦的效应与相关药物进行了比较。总之，我们过去几年对抗病毒药物的研究表明，体内和体外方法绝不是相互竞争的，并且两种方法的结合可为毒理学评估提供坚实的基础。
