Carcinogen-Induced Model of Proangiogenesis in Zebrafish Embryo-Larvae.

Abstract

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.