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致畸生物标志物:来自动物研究的建议。

Biomarkers of teratogenesis: suggestions from animal studies.

机构信息

Università di Milano, Department of Biology, Italy.

出版信息

Reprod Toxicol. 2012 Sep;34(2):180-5. doi: 10.1016/j.reprotox.2012.05.003. Epub 2012 May 18.

Abstract

Biomarkers of effect are measurable biochemical, physiological or other alterations within an organism that can be recognized as causing an established or potential impairment of embryo-fetal development. They may be identified studying the mechanisms of action of teratogens. Hyperacetylation of histones, oxidative stress, cholesterol and retinoic acid unbalance are some of the identified mechanisms of action of some known teratogens. Nevertheless, their use is not currently applicable in human pregnancy because of the difficulty of the choice of biological material, the time when the material must be obtained, and the invasivity of methods. Furthermore, before using them in human pregnancy studies, biomarkers should be validated in experimental animals and in epidemiologic studies. On the contrary, some biomarkers could be useful in the screening of developmental toxicity of chemicals and drugs, comparing molecules of the same chemical class or with the similar pharmacologic activity, and using adequate in vitro tests, in order to reduce the use of experimental animals.

摘要

效应生物标志物是指在生物体中可识别的、能引起胚胎-胎儿发育损害的确立或潜在的生化、生理或其他改变。可以通过研究致畸物的作用机制来识别它们。组蛋白乙酰化、氧化应激、胆固醇和视黄酸失衡是一些已知致畸物的已确定作用机制。然而,由于生物材料选择的困难、获得材料的时间以及方法的侵入性,它们目前在人类妊娠中无法应用。此外,在将其用于人类妊娠研究之前,应在实验动物和流行病学研究中验证生物标志物。相反,一些生物标志物在筛选化学物质和药物的发育毒性方面可能有用,比较同一化学类别的分子或具有相似的药理活性,并使用适当的体外试验,以减少实验动物的使用。

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