Kraft J C, Kimelman D, Juchau M R
Department of Pharmacology, University of Washington, Seattle 98195.
Drug Metab Dispos. 1995 Jan;23(1):72-82.
Recently, the temporal and spatial distribution patterns of two established, endogenous retinoid receptor ligands, 9-cis-retinoic acid and all-trans-retinoic acid and various precursor retinoids were described in Xenopus embryos during early development (Creech Kraft et al., Proc. Natl. Acad. Sci. U.S.A. 1994; Biochem. J. 1994). Each of these two receptor ligands is a metabolite of vitamin A (all-trans-retinol), and each is also a potent dysmorphogen in Xenopus embryos as well as in embryos of several other vertebrate species. This study demonstrates early embryonic metabolism of exogenous all-trans-retinol, 9-cis-retinol, all-trans-retinal, and 9-cis-retinal to 9-cis-retinoic acid, all-trans-retinoic acid, and other metabolites in Xenopus embryos during neurulation, a specific stage of development that spans a time period of approximately 8 hr. Our results demonstrate that the Xenopus embryo provides a suitable model system for studying the embryonic bioconversion of retinoids and dysmorphogenic effects within a single time window of development.
最近，在非洲爪蟾胚胎早期发育过程中，描述了两种已确定的内源性类视黄醇受体配体——9-顺式视黄酸和全反式视黄酸以及各种前体类视黄醇的时空分布模式（克里奇·克拉夫特等人，《美国国家科学院院刊》1994年；《生物化学杂志》1994年）。这两种受体配体均为维生素A（全反式视黄醇）的代谢产物，并且在非洲爪蟾胚胎以及其他几种脊椎动物胚胎中均为强效致畸剂。本研究表明，在神经胚形成期（发育的一个特定阶段，持续约8小时），非洲爪蟾胚胎可将外源性全反式视黄醇、9-顺式视黄醇、全反式视黄醛和9-顺式视黄醛早期代谢为9-顺式视黄酸、全反式视黄酸和其他代谢产物。我们的结果表明，非洲爪蟾胚胎为在单一发育时间窗口内研究类视黄醇的胚胎生物转化和致畸作用提供了一个合适的模型系统。
