RT Journal Article T1 Plastics in Cyanobacterial Blooms—Genotoxic E ects of Binary Mixtures of Cylindrospermopsin and Bisphenols in HepG2 Cells A1 Hercog, Klara A1 Stern, Alja A1 Maisanaba, Sara A1 Filipic, Metka A1 Zegura, Bojana K1 Cylindrospermopsin K1 CYN K1 Bisphenols K1 BPA K1 BPS K1 BPF K1 BPAF K1 Co-exposure K1 Genotoxicity K1 Cytotoxicity AB Ever-expanding environmental pollution is causing a rise in cyanobacterial bloomsand the accumulation of plastics in water bodies. Consequently, exposure to mixtures ofcyanotoxins and plastic-related contaminants such as bisphenols (BPs) is of increasing concern.The present study describes genotoxic e ects induced by co-exposure to one of the emergingcyanotoxins—cylindrospermopsin (CYN)—(0.5 g/mL) and BPs (bisphenol A (BPA), S (BPS), andF (BPF); (10 g/mL)) in HepG2 cells after 24 and 72 h of exposure. The cytotoxicity was evaluatedwith an MTS assay and genotoxicity was assessed through the measurement of the induction of DNAdouble strand breaks (DSB) with the H2AX assay. The deregulation of selected genes (xenobioticmetabolic enzyme genes, DNA damage, and oxidative response genes) was assessed using qPCR.The results showed a moderate reduction of cell viability and induction of DSBs after 72 h of exposureto the CYN/BPs mixtures and CYN alone. None of the BPs alone reduced cell viability or inducedDSBs. No significant di erence was observed between CYN and CYN/BPs exposed cells, except withCYN/BPA, where the antagonistic activity of BPA against CYN was indicated. The deregulation ofsome of the tested genes (CYP1A1, CDKN1A, GADD45A, and GCLC) was more pronounced afterexposure to the CYN/BPs mixtures compared to single compounds, suggesting additive or synergisticaction. The present study confirms the importance of co-exposure studies, as our results showpollutant mixtures to induce e ects di erent from those confirmed for single compounds. PB MDPI YR 2020 FD 2020-03-31 LK https://hdl.handle.net/10433/19729 UL https://hdl.handle.net/10433/19729 LA en NO Toxins 2020, 12, 219 NO This research was funded by the Slovenian Research Agency [research core funding P1-0245, and PhD grant to Klara Hercog MR36321], and the PhD grant from the University of Seville to the Sara Maisanaba (VI PPIT, I.3A1, 2017) and the COST Actions ES1105 (Cyanobacterial blooms and toxins in water resources: Occurrence, impacts and management). NO National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, Veˇcna pot 111, 1000 Ljubljana, Slovenia NO Area of Toxicology, Department of Molecular Biology and Biochemistry Engineering, University Pablo de Olavide DS RIO RD Apr 25, 2026