Effect of acyclovir on mammalian embryonic development in culture

Abstract

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] interfered with embryonic development in vitro when assessed with the "whole-embryo" culture technique. The "no-observed-effect level" was at 10 microM acyclovir; Minor impairment of embryonic development (retarded development of ear anlagen) was observed in vitro at 25 microM acyclovir in the culture medium. At high concentrations (100 or 200 microM) development of the ear anlagen was largely inhibited. At concentrations of 50 microM acyclovir or higher, additional disturbances of embryonic differentiation in vitro became obvious, resulting in gross structural abnormalities, especially of the brain (telencephalon); Histological examinations confirmed and extended these observations: at 100 microM acyclovir alterations of the neuroepithelium of the ventricles were pronounced, the telencephalon had developed poorly or was almost completely absent, and necroses were seen in the ear anlagen, the maxillary branch and within the somites; In a limb bud culture (mouse embryos, starting with day 11 of gestation) acyclovir interfered with the differentiation of cartilaginous bone anlagen at concentrations of 200 microM and more in the culture medium. A concentration of 100 microM induced no significant effect. Thus, this organ culture system is less sensitive to the action of acyclovir when compared with whole-embryo culture; Contrary to the results achieved with acyclovir, physiological nucleosides (2'-deoxyguanosine and 2'-deoxyadenosine) did not interfere with embryonic development in vitro even at the highest concentration tested (500 microM).