Inhibition of DNA synthesis in mouse whole embryo culture by 2-methoxyacetic acid and attenuation of the effects by simple physiological compounds.

Gestation day 11 CD-1 mouse embryos were cultured in serum containing or serum-free media for 6 h in the presence of 2-methoxyacetic acid (2-MAA), the proximate teratogen arising from 2-methoxyethanol. The rate of DNA synthesis was determined following exposure of embryos to [3H]thymidine during the final hour of culture. 2-MAA (25 mM) produced a 50% reduction of [3H]thymidine incorporation into embryos cultured in serum-containing medium, whereas only 5 mM 2-MAA were required for a similar inhibitory effect in embryos cultured in serum-free medium. When embryos were concomitantly exposed to 2-MAA (5 mM) and to formate (1 mM), acetate (5 mM), or sarcosine (2 mM), a significant attenuation of the 2-MAA-induced inhibition of [3H]thymidine incorporation occurred. The findings suggest that these agents, which also attenuated developmental toxicity in vivo, may compete with 2-MAA actions which inhibit DNA synthesis in the embryo.