R. Stahlmann et al., SIGNIFICANCE OF EMBRYO CULTURE METHODS FOR STUDYING THE PRENATAL TOXICITY OF VIRUSTATIC AGENTS, Reproductive toxicology, 7, 1993, pp. 129-143
Culture methods have become important tools for elucidating the prenat
al toxicity of drugs and other xenobiotics. In this paper we will revi
ew how we used in vitro as well as in vivo approaches to demonstrate t
he teratogenic potential of aciclovir and other related virustatic age
nts. In addition, some new data on this topic will be given. The terat
ogenic potential of the virustatic agent aciclovir was not recognized
in routinely performed segment-II-studies, but the first indication ca
me 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 high
est 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 aga
in the effect of aciclovir could be compared with related drugs. In su
mmary, 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 toxico
logic evaluation.