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N-nitrosodimethylamine exposure to zebrafish embryos/larvae causes cardiac and spinal developmental toxicity
Comparative Biochemistry and Physiology C: Toxicology & Pharmacology ( IF 3.9 ) Pub Date : 2023-12-27 , DOI: 10.1016/j.cbpc.2023.109823
Xiaoyi Liu , Jinge Song , Xiaotao Yan , Pingping Li , Jinhua Zhang , Bin Wang , Jing Si , Yong Chen

N-nitrosodimethylamine (NDMA), one of the new nitrogen-containing disinfection by-products, is potentially cytotoxic, genotoxic, and carcinogenic. Its potential toxicological effects have attracted a wide range of attention, but the mechanism is still not sufficiently understood. To better understand the toxicological mechanisms of NDMA, zebrafish embryos were exposed to NDMA from 3 h post-fertilization (hpf) to 120hpf. Mortality and malformation were significantly increased, and hatching rate, heart rate, and swimming behavior were decreased in the exposure groups. The result indicated that NDMA exposure causes cardiac and spinal developmental toxicity. mRNA levels of genes involved in the apoptotic pathway, including p53, bax, and bcl-2 were significantly affected by NDMA exposure. Moreover, the genes associated with spinal and cardiac development (myh6, myh7, nkx2.5, eph, bmp2b, bmp4, bmp9, run2a, and run2b) were significantly downregulated after treatment with NDMA. Wnt and TGF-β signaling pathways, crucial for the development of diverse tissues and organs in the embryo and the establishment of the larval spine, were also significantly disturbed by NDMA treatment. In summary, the disinfection by-product, NDMA, exhibits spinal and cardiac developmental toxicity in zebrafish embryos, providing helpful information for comprehensive analyses and a better understanding the mechanism of its toxicity.



中文翻译:

斑马鱼胚胎/幼虫接触 N-亚硝基二甲胺会导致心脏和脊髓发育毒性

N-亚硝基二甲胺 (NDMA) 是一种新型含氮消毒副产物,具有潜在的细胞毒性、遗传毒性和致癌性。其潜在的毒理学作用已引起广泛关注,但其机制仍不充分了解。为了更好地了解 NDMA 的毒理学机制,将斑马鱼胚胎从受精后 3 小时 (hpf) 到 120hpf 暴露于 NDMA。暴露组的死亡率和畸形率显着增加,孵化率、心率和游泳行为下降。结果表明,NDMA 暴露会导致心脏和脊髓发育毒性。NDMA 暴露显着影响参与凋亡途径的基因(包括p53baxbcl-2 )的 mRNA 水平。此外,与脊柱和心脏发育相关的基因(myh6myh7nkx2.5ephbmp2bbmp4bmp9run2arun2b )在 NDMA 治疗后显着下调。Wnt 和 TGF-β 信号通路对于胚胎中多种组织和器官的发育以及幼虫脊柱的建立至关重要,也受到 NDMA 处理的显着干扰。总之,消毒副产物NDMA对斑马鱼胚胎表现出脊髓和心脏发育毒性,为综合分析和更好地理解其毒性机制提供了有用的信息。

更新日期:2024-01-01
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