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Carcinogen‐Induced Model of Proangiogenesis in Zebrafish Embryo‐Larvae

机译:斑马鱼胚胎幼虫中致癌癌诱导模型

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Tumor angiogenesis is the main target in cancer drug development. Discovery of antiangiogenic agents targeting different mechanisms of action is the major area of research to control tumor growth and metastasis. Zebrafish (in the embryo-larvae stage) acts as an essential preclinical efficacy-toxicity model for antiangiogenic drug discovery. We aimed to develop a carcinogen-induced model of proangiogenesis in zebrafish embryo-larvae using the carcinogens lindane and benzo[a]pyrene. Zebrafish were randomly selected for mating. Postspawning, healthy embryos were staged, dispensed in reverse-osmosis water in a 12-well plate, and incubated at 28.5 degrees C, wherein 24 h postfertilization they were exposed to sublethal concentrations of the carcinogens. Three days postexposure, embryos were stained with alkaline phosphatase, and the angiogenic basket was imaged using a bright-field microscope. The number of subintestinal vessels, their length from somite to the basket, and other proangiogenic parameters were measured and analyzed. The effective concentrations causing a 30% increase in subintestinal vessels for benzo[a]pyrene and lindane were 2.69 and 2.24 mu M, respectively, thus proving their proangiogenic potency. The carcinogen-induced model of proangiogenesis in zebrafish embryo-larvae can be used as an effective high-throughput screening tool to assess the proangiogenic potential of carcinogenic compounds and to screen antiangiogenic drugs for better therapeutic intervention. Environ Toxicol Chem 2020;00:1-7.(c) 2020 SETAC
机译:肿瘤血管生成是癌症药物发育的主要靶标。发现针对不同行动机制的抗血管生成剂是控制肿瘤生长和转移的主要研究领域。斑马鱼(在胚胎幼虫阶段)起到抗血管生成药物发现的基本临床前疗效模型。我们旨在使用致癌林丹和苯并[a]芘在斑马鱼胚胎幼虫中发育致癌诱导的雌激素模型。斑马鱼被随机选择交配。术后术,健康胚胎被分配,在12孔板中分配在反渗透水中,并在28.5℃下孵育,其中将它们暴露于致致致致致致癌致癌浓度的致癌物质。曝光三天后,用碱性磷酸酶染色胚胎,使用亮场显微镜对血管生成篮进行成像。测量并分析了局部血管的数量,从一定的篮子的长度以及其他常规发生参数。产生苯并[a]芘和林丹的子宫子血管增加30%的有效浓度分别为2.69和2.24μm,从而证明它们的致致效力。斑马鱼胚胎幼虫中的致癌致癌模型可用作有效的高通量筛选工具,以评估致癌化合物的常规潜力和筛选抗血管生成药物以进行更好的治疗介入。环境毒素化学2020; 00:1-7。(c)2020 setac

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