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Analysis of the activity of DNA, RNA, and protein synthesis inhibitors onXenopusembryo development

机译:DNA、RNA和蛋白质合成抑制剂对非洲爪蟾胚胎发育的活性分析

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AbstractThe teratogenic and growth‐inhibiting potential of DNA, RNA, and protein synthesis inhibitors was explored using the Frog Embryo Teratogenesis Assay:Xenopus(FETAX). Endpoints measured in 96‐h static tests were survival, malformation, ability to swim, skin pigmentation, stage of development, and growth. The DNA synthesis inhibitors hydroxyurea, cytosine arabinoside, and ethidium bromide proved to be teratogenic by the severity of malformations induced. Hydroxyurea gave an LC50of 1.82 mg/ml, an EC50(malformation) of 0.43 mg/ml, while the values for cytosine arabinsode were 5.41 and 0.76, respectively. The values for ethidium bromide were 0.05 and 0.035. The RNA synthesis inhibitor actinomycin D and the protein synthesis inhibitor cycloheximide were more embryolethal than teratogenic but significantly inhibited growth as determined by head‐tail length measurements. Actinomycin D caused severe malformations, while cycloheximide caused relatively minor abnormalities. The LC50for actinomycin D was 1.89 mg/ml, while the EC50(malformation) was 2.17 mg/ml. For cycloheximide, the values were 1.59 and 1.19, respectively. FETAX advantages include rapid data collection, the ability to measure stage‐dependent effects, and the ability to use a large number of embryos to obtain excellent doseresponse curves with narrow confidence limits. Disadvantages include lack of a metabolic activation system, absence of a placental relationship, and the inability to detect specific abnormalities such as limb defects
机译:摘要采用蛙胚畸形试验:非洲爪蟾(FETAX)探究DNA、RNA和蛋白质合成抑制剂的致畸和生长抑制潜力。在96小时静态测试中测量的终点是存活率、畸形、游泳能力、皮肤色素沉着、发育阶段和生长。DNA 合成抑制剂羟基脲、胞嘧啶阿拉伯糖苷和溴化乙锭被证明因诱发畸形的严重程度而致畸。羟基脲的LC50为1.82 mg/ml,EC50(畸形)为0.43 mg/ml,而胞嘧啶阿拉伯糖的浓度值分别为5.41和0.76。溴化乙锭的值分别为0.05和0.035。RNA合成抑制剂放线菌素D和蛋白质合成抑制剂环己酰亚胺的胚胎致死率高于致畸性,但通过头尾长度测量确定,可显着抑制生长。放线菌素D引起严重畸形,而环己酰亚胺引起相对轻微的异常。放线菌素D的LC50为1.89 mg/ml,EC50(畸形)为2.17 mg/ml。对于环己酰亚胺,值分别为1.59和1.19。FETAX的优势包括快速数据收集、测量阶段依赖性效应的能力,以及使用大量胚胎获得具有窄置信限的出色剂量反应曲线的能力。缺点包括缺乏代谢激活系统、缺乏胎盘关系以及无法检测特定异常(如肢体缺陷)

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