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 °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 µM, 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 2021;40:447–453.© 2020 SETAC

中文翻译：

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致癌物诱导的斑马鱼胚胎幼虫促血管生成模型

肿瘤血管生成是癌症药物开发的主要目标。发现针对不同作用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（处于胚胎-幼虫阶段）作为抗血管生成药物发现的重要临床前功效-毒性模型。我们的目的是使用致癌物质林丹和苯并[ a]芘。斑马鱼是随机选择交配的。产卵后，健康胚胎被分阶段，分配在 12 孔板中的反渗透水中，并在 28.5 °C 下孵育，其中受精后 24 小时它们暴露于亚致死浓度的致癌物。暴露三天后，胚胎用碱性磷酸酶染色，血管生成篮使用明视野显微镜成像。测量和分析肠下血管的数量、它们从体节到篮的长度以及其他促血管生成参数。导致肠下血管中苯并 [ a]增加 30% 的有效浓度]芘和林丹的浓度分别为 2.69 和 2.24 µM，从而证明了它们的促血管生成效力。斑马鱼胚胎幼虫致癌物诱导的促血管生成模型可作为一种有效的高通量筛选工具，用于评估致癌化合物的促血管生成潜力，并筛选抗血管生成药物以进行更好的治疗干预。环境毒理学化学2021；40:447–453。© 2020 SETAC