State Environmental Protection Key Laboratory of All Material Fluxes in River Ecosystems, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China; The Key Laboratory of Water and Sediment Sciences, Ministry of Education, Beijing 100871, China.
State Environmental Protection Key Laboratory of All Material Fluxes in River Ecosystems, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China; The Key Laboratory of Water and Sediment Sciences, Ministry of Education, Beijing 100871, China.
Aquat Toxicol. 2023 May;258:106495. doi: 10.1016/j.aquatox.2023.106495. Epub 2023 Mar 14.
Fluoroquinolones (FQs) are known to have genotoxicity to aquatic organisms. However, their genotoxicity mechanisms, individually and in combination with heavy metals, are poorly understood. Here, we investigated the single and joint genotoxicity of FQs, ciprofloxacin (CIP) and enrofloxacin (ENR), and metals (Cd and Cu) at environmentally relevant concentrations (0.2 µM) to zebrafish embryos. We found that FQs or/and metals induced genotoxicity (i.e., DNA damage and cell apoptosis) to zebrafish embryos. Compared with their single exposure, the combined exposure of FQs and metals elicited less ROS overproduction but higher genotoxicity, suggesting other toxicity mechanisms may also act in addition to oxidation stress. The upregulation of nucleic acid metabolites and the dysregulation of proteins confirmed the occurrence of DNA damage and apoptosis, and further revealed the inhibition of DNA repair by Cd and binding of DNA or DNA topoisomerase by FQs. This study deepens the knowledge on the responses of zebrafish embryos to exposure of multiple pollutants, and highlights the genotoxicity of FQs and heavy metals to aquatic organisms.
氟喹诺酮类（FQs）已知对水生生物具有遗传毒性。然而，它们的遗传毒性机制，无论是单独作用还是与重金属联合作用，都知之甚少。在这里，我们研究了氟喹诺酮类药物（环丙沙星（CIP）和恩诺沙星（ENR））和金属（Cd 和 Cu）在环境相关浓度（0.2µM）下对斑马鱼胚胎的单一和联合遗传毒性。我们发现 FQs 或/和金属会引起斑马鱼胚胎的遗传毒性（即 DNA 损伤和细胞凋亡）。与单一暴露相比，FQs 和金属的联合暴露会产生较少的 ROS 过度产生，但遗传毒性更高，这表明除了氧化应激之外，可能还有其他毒性机制起作用。核酸代谢物的上调和蛋白质的失调证实了 DNA 损伤和凋亡的发生，并进一步揭示了 Cd 对 DNA 修复的抑制和 FQs 对 DNA 或 DNA 拓扑异构酶的结合。这项研究深化了我们对多种污染物暴露下斑马鱼胚胎反应的认识，并强调了 FQs 和重金属对水生生物的遗传毒性。
