Dictyostelium discoideum: An Alternative Nonanimal Model for Developmental Toxicity Testing.
Dictyostelium discoideum: An Alternative Nonanimal Model for Developmental Toxicity Testing.
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DICSYOSTELIUM DISCOIDEUM：一种用于发育毒性测试的替代非动物模型。
DOI：
10.1093/toxsci/kfab097
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发表时间：
2021-09-28
期刊：
影响因子：
--
通讯作者：
Thompson CRL
中科院分区：
文献类型：
--
作者：
Baines RP;Wolton K;Thompson CRL
毒性评价的一个关键方面是发育和生殖毒性（DART）测试。传统上，DART测试已经在哺乳动物模型系统中在体内进行。新的立法旨在减少动物使用和与DART测试相关的高昂成本，以及需要了解发育毒性的遗传途径，这意味着对替代模型系统的需求日益增长。在这里，我们探讨的潜力，真核社会阿米巴Dictyosteoba discoideum，这已经被广泛用作一个简单的模型系统的细胞和发育生物学，作为一个潜在的非动物模型的DART测试。我们开发了用于高通量筛选D.盘状花序生长发育。这使得广泛的测试化合物的毒性被表征，这表明D。discoideum可以广泛预测哺乳动物毒性。此外，我们表明，该系统可用于进行功能基因组筛选，以比较不同化合物的分子作用模式。例如，对影响锂和丙戊酸毒性的突变进行全基因组筛选，可以确定共同和独特的生物靶点以及介导其毒性的分子过程。这些研究表明D.由于discoideum对高通量方法的适应性和分子遗传可追踪性，它可以代表DART测试的预测性非动物模型。
A critical aspect of toxicity evaluation is developmental and reproductive toxicity (DART) testing. Traditionally, DART testing has been conducted in vivo in mammalian model systems. New legislation aimed at reducing animal use and the prohibitive costs associated with DART testing, together with a need to understand the genetic pathways underlying developmental toxicity means there is a growing demand for alternative model systems for toxicity evaluation. Here we explore the potential of the eukaryotic social amoeba Dictyostelium discoideum, which is already widely used as a simple model system for cell and developmental biology, as a potential nonanimal model for DART testing. We developed assays for high-throughput screening of toxicity during D. discoideum growth and development. This allowed the toxicity of a broad range of test compounds to be characterized, which revealed that D. discoideum can broadly predict mammalian toxicity. In addition, we show that this system can be used to perform functional genomic screens to compare the molecular modes of action of different compounds. For example, genome-wide screens for mutations that affect lithium and valproic acid toxicity allowed common and unique biological targets and molecular processes mediating their toxicity to be identified. These studies illustrate that D. discoideum could represent a predictive nonanimal model for DART testing due to its amenability to high-throughput approaches and molecular genetic tractability.
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DOI：
10.1016/j.reprotox.2014.09.005
发表时间：
2015-08-01
期刊：
Reproductive toxicology (Elmsford, N.Y.)
影响因子：
--
作者：
Ducharme NA;Reif DM;Gustafsson JA;Bondesson M
通讯作者：
Bondesson M
影响因子：
3.3
作者：
Gustafson, A. -L.;Stedman, D. B.;Augustine-Rauch, K. A.
通讯作者：
Augustine-Rauch, K. A.
影响因子：
3.7
作者：
Ali S;van Mil HG;Richardson MK
通讯作者：
Richardson MK
影响因子：
--
作者：
Liao XH;Kimmel AR
通讯作者：
Kimmel AR
影响因子：
14.8
作者：
Fey, Petra;Kowal, Anthony S.;Chisholm, Rex L.
通讯作者：
Chisholm, Rex L.