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. 2019 Oct:233:336-346.
doi: 10.1016/j.chemosphere.2019.05.261. Epub 2019 Jun 1.

Developmental toxicity and alteration of gene expression in zebrafish embryo exposed to 6-benzylaminopurine

Weixiang Wang  1 , Binrong Wang  2 , Zihao Liu  2 , Xuemei Xia  2
Affiliations

Developmental toxicity and alteration of gene expression in zebrafish embryo exposed to 6-benzylaminopurine

Weixiang Wang et al. Chemosphere. 2019 Oct.

Abstract

6-benzylaminopurine (6-BA) is widely used in agriculture and horticulture as plant growth regulator. Its excessive use may pose a potential risk to both environment and human health, which is causing great concern. This study was undertaken to assess the acute developmental toxicity of 6-BA to zebrafish embryos based on OECD protocols and mortality, hatching rate and malformation were investigated. Results showed that the 96 h-LC50 and 96 h- EC50 values were 63.29 mg/L and 41.86 mg/L, respectively. No mortality or teratogenic effects were found at concentrations lower than 10 mg/L 6-BA at concentrations higher than 50 mg/L significantly inhibited hatchability and embryo development, induced serious toxicity characterized by morphologic abnormalities (elongated pericardium, heart and yolk sac edema, spine curvature) and functional failure (slow spontaneous movement and heart rate, growth retardation, yolk sac absorption retention). Moreover, 6-BA-induced apoptosis was observed in embryos by the acridine orange staining and confirmed by the apoptotic-related genes, all of which p53 was significantly up-regulated at concentrations higher than 10 mg/L, bax at concentrations higher than 12.5 mg/L, while bcl2 was down-regulated at concentrations higher than 25 mg/L. As for genes of cardiac development, qPCR results demonstrated that nkx2.5, gata5, and amhc were significantly down-regulated at concentrations higher than 25 mg/L, vmhc and atp2a2a at concentration of 50 mg/L, in contrast, hand2 was up-regulated at concentration of 50 mg/L. Our data indicate that 6-BA induces a dose-dependent toxicity resulting in apoptosis through the involvement of p53-dependent pathways and hindering normal heart development in zebrafish embryos.

Keywords: 6-Benzylaminopurine (6-BA); Cardiac toxicity; Developmental toxicity; Teratogenic effect; Zebrafish.

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