Single and combined genotoxicity of metals and fluoroquinolones to zebrafish embryos at environmentally relevant concentrations

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.