Analysis of the activity of DNA, RNA, and protein synthesis inhibitors on Xenopus embryo development.
The 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 LC50 of 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 LC50 for 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 dose-response 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 in 96 h.
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D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000818:Animals; D003513:Cycloheximide / Q000633:toxicity*; D003561:Cytarabine / Q000633:toxicity*; D004261:DNA Replication / Q000187:drug effects; D003609:Dactinomycin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D004996:Ethidium / Q000633:toxicity*; D005260:Female; D006918:Hydroxyurea / Q000633:toxicity*; D014176:Protein Biosynthesis / Q000187:drug effects; D013723:Teratogens; D014158:Transcription, Genetic / Q000187:drug effects; D014981:Xenopus / Q000196:embryology*
D013723:Teratogens; D003561:Cytarabine; D003609:Dactinomycin; D003513:Cycloheximide; D004996:Ethidium; D006918:Hydroxyurea