有害的蓝藻水华由于产生诸如微囊藻毒素等危险的次生代谢产物而引起了许多生物安全事件。此外，蓝藻还释放出许多其他未经探索的成分。我们在一种优势、盛开的种类——毛细蓝藻中鉴定出一种有毒混合物，并发现植物鞘氨醇（PHS）是其中的一种生物活性成分。由于PHS表现出毒性，并被欧洲化学品管理局认为是一种危险物质，我们假设PHS可能是毛细蓝藻外泌物中的一种潜在有毒化合物。然而，PHS生态毒性的机理仍不清楚。我们使用八种人类细胞系的体外细胞模型评估了PHS的细胞毒性，并观察到鼻咽癌细胞系CNE2最为敏感。我们将CNE2细胞暴露于0-25µmol/L的PHS中，持续24小时以探究其毒性和机制。PHS暴露导致了异常的核形态、微核和DNA损伤。此外，PHS显著抑制了细胞增殖并阻滞了细胞周期在S期。Western blot的结果表明，PHS增加了DNA损伤相关蛋白（ATM、p-P53和P21）的表达，并减少了S期相关蛋白（CDK2、CyclinA2和CyclinE1）的表达，表明了PHS对CNE2细胞的毒理机制。这些数据提供了证据表明，PHS具有遗传毒性，并通过破坏DNA抑制细胞增殖。我们的研究提供了证据表明，PHS通过破坏DNA抑制细胞增殖。虽然还需要进一步的研究，但我们提出，除了其他已经确定的次生化合物之外，PHS应被视为毛细蓝藻外泌物中的一种潜在有毒成分。版权所有©2023作者。由爱思唯尔公司出版。保留所有权利。

Harmful cyanobacterial blooms have caused numerous biosecurity incidents owing to the production of hazardous secondary metabolites such as microcystin. Additionally, cyanobacteria also release many other components that have not been explored. We identified compounds of a toxic mixture exudated from a dominant, blooming species, Microcystis aeruginosa, and found that phytosphingosine (PHS) was one of the bioactive components. Since PHS exhibited toxicity and is deemed a hazardous substance by the European Chemicals Agency, we hypothesized that PHS is a potentially toxic compound in M. aeruginosa exudates. However, the mechanisms of PHS ecotoxicity remain unclear. We assessed the cytotoxicity of PHS using an in vitro cell model in eight human cell lines and observed that the nasopharyngeal carcinoma cell line CNE2 was the most sensitive. We exposed CNE2 cells to 0-25 µmol/L PHS for 24 hr to explore its toxicity and mechanism. PHS exposure resulted in abnormal nuclear morphology, micronuclei, and DNA damage. Moreover, PHS significantly inhibited cell proliferation and arrested cell cycle at S phase. The results of Western blot suggested that PHS increased the expression of DNA damage-related proteins (ATM, p-P53 and P21) and decreased the expression of S phase-related proteins (CDK2, CyclinA2 and CyclinE1), indicating the toxicological mechanism of PHS on CNE2 cells. These data provide evidence that PHS has genetic toxicity and inhibits cell proliferation by damaging DNA. Our study provides evidence that PHS inhibits cell proliferation by damaging DNA. While additional work is required, we propose that PHS been considered as a potentially toxic component in MaE in addition to other well-characterized secondary compounds.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.