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Ancient Sturgeons Possess Effective DNA Repair Mechanisms: Influence of Model Genotoxicants on Embryo Development of Sterlet

机译:古代鲟鱼具有有效的DNA修复机制:模型遗传毒剂对甾体胚胎发育的影响

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摘要

DNA damage caused by exogenous or endogenous factors is a common challenge for developing fish embryos. DNA damage repair (DDR) pathways help organisms minimize adverse effects of DNA alterations. In terms of DNA repair mechanisms, sturgeons represent a particularly interesting model due to their exceptional genome plasticity. Sterlet (Acipenser ruthenus) is a relatively small species of sturgeon. The goal of this study was to assess the sensitivity of sterlet embryos to model genotoxicants (camptothecin, etoposide, and benzo[a]pyrene), and to assess DDR responses. We assessed the effects of genotoxicants on embryo survival, hatching rate, DNA fragmentation, gene expression, and phosphorylation of H2AX and ATM kinase. Exposure of sterlet embryos to 1 µM benzo[a]pyrene induced low levels of DNA damage accompanied by ATM phosphorylation and xpc gene expression. Conversely, 20 µM etoposide exposure induced DNA damage without activation of known DDR pathways. Effects of 10 nM camptothecin on embryo development were stage-specific, with early stages, before gastrulation, being most sensitive. Overall, this study provides foundational information for future investigation of sterlet DDR pathways.
机译:外源性或内源性因素引起的DNA损害是培养鱼胚的常见挑战。 DNA损伤修复(DDR)途径有助于生物体最小化DNA改变的不良影响。就DNA修复机制而言,由于其特殊的基因组可塑性,梯形代表了特别有趣的模型。甾体(acipenser ruthenus)是一种相对较小的鲟鱼。本研究的目的是评估甾体胚胎对模型遗传毒剂的敏感性(喜树碱,依托泊苷和苯并[a]芘),并评估DDR反应。我们评估了基因毒剂对H2AX和ATM激酶的胚胎存活,阴影率,DNA碎片,基因表达和磷酸化的影响。甾体胚胎暴露于1μm苯并[a]芘诱导伴随ATM磷酸化和XPC基因表达的低水平DNA损伤。相反,20μm依常皂苷暴露诱导DNA损伤而不激活已知的DDR途径。 10nm camptothecin对胚胎发育的影响是阶段特异性的,早期阶段,腐殖质之前是最敏感的。总体而言,本研究提供了未来调查Etclet DDR途径的基础信息。

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