Significance of embryo culture methods for studying the prenatal toxicity of virustatic agents.
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.
Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Germany.
R
R
Stahlmann
S
S
Klug
M
M
Foerster
D
D
Neubert
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D002478:Cells, Cultured; D046508:Culture Techniques; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005260:Female; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014116:Toxicology / Q000379:methods*
D000998:Antiviral Agents