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2-甲氧基乙酸对小鼠全胚胎培养中DNA合成的抑制作用以及简单生理化合物对该作用的减弱

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

作者信息

Stedman D B, Welsch F

机构信息

Department of Biochemical Toxicology and Pathobiology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.

出版信息

Toxicol Lett. 1989 Jan;45(1):111-7. doi: 10.1016/0378-4274(89)90165-3.

DOI:10.1016/0378-4274(89)90165-3
PMID:2464863
Abstract

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.

摘要

妊娠第11天的CD-1小鼠胚胎在含有2-甲氧基乙酸(2-MAA)(2-甲氧基乙醇产生的直接致畸剂)的含血清或无血清培养基中培养6小时。在培养的最后一小时,胚胎暴露于[3H]胸苷后测定DNA合成速率。2-MAA(25 mM)使在含血清培养基中培养的胚胎中[3H]胸苷掺入量降低50%,而在无血清培养基中培养的胚胎中,仅需5 mM 2-MAA就能产生类似的抑制作用。当胚胎同时暴露于2-MAA(5 mM)和甲酸盐(1 mM)、乙酸盐(5 mM)或肌氨酸(2 mM)时,2-MAA诱导的[3H]胸苷掺入抑制作用显著减弱。这些发现表明,这些在体内也能减轻发育毒性的物质,可能与抑制胚胎DNA合成的2-MAA作用相互竞争。

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