Löwkvist B, Emanuelsson H, Egyházi E, Sjöberg J, Långström E, Heby O
Dev Biol. 1986 Aug;116(2):291-301. doi: 10.1016/0012-1606(86)90132-6.
In the early chick embryo, inhibition of polyamine synthesis by alpha-difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, blocks development at gastrulation. This effect was paralleled by a marked suppression of RNA and protein synthesis. There was no major change in cell cycle distribution in DFMO-treated embryos. Nevertheless, analysis of DNA synthesis and mitotic index indicated a prolongation of the cell cycle, possibly affecting all the phases. The inhibition of RNA synthesis in polyamine-depleted embryos, as evaluated by [3H]uridine incorporation, was not a result of reduced uptake or expansion of the UTP pool, and there was no deficiency or major imbalance among the ATP, GTP, and CTP pools. On the basis of agarose gel electrophoretic analyses of the various RNA species, and experiments using RNA synthesis inhibitors with different modes of action (actinomycin D, alpha-amanitin, and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole), it was concluded that the DFMO-induced gastrular arrest was due to general inhibition of transcription.
在鸡胚发育早期，α-二氟甲基鸟氨酸（DFMO）作为鸟氨酸脱羧酶的一种酶激活不可逆抑制剂，抑制多胺合成，会在原肠胚形成阶段阻断胚胎发育。这种效应伴随着RNA和蛋白质合成的显著抑制。在经DFMO处理的胚胎中，细胞周期分布没有重大变化。然而，对DNA合成和有丝分裂指数的分析表明细胞周期延长，可能影响所有阶段。通过[3H]尿苷掺入评估，多胺缺乏胚胎中RNA合成的抑制并非UTP池摄取减少或扩大的结果，并且ATP、GTP和CTP池之间没有缺乏或重大失衡。基于对各种RNA种类的琼脂糖凝胶电泳分析，以及使用具有不同作用模式的RNA合成抑制剂（放线菌素D、α-鹅膏蕈碱和5,6-二氯-1-β-D-呋喃核糖基苯并咪唑）进行的实验，得出结论：DFMO诱导的原肠胚停滞是由于转录的普遍抑制。
