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.
Stedman
D B
DB
Department of Biochemical Toxicology and Pathobiology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
Welsch
F
F
D000085:Acetates / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects; D046508:Culture Techniques; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005026:Ethylene Glycols / Q000633:toxicity; D005561:Formates / Q000494:pharmacology; D051379:Mice; D012521:Sarcosine / Q000494:pharmacology; D013723:Teratogens; D013936:Thymidine / Q000378:metabolism
D000085:Acetates; D005026:Ethylene Glycols; D005561:Formates; D013723:Teratogens; C030544:formic acid; D004247:DNA; C005219:methyl cellosolve; C013598:methoxyacetic acid; D013936:Thymidine; D012521:Sarcosine