20.500.12556/DiRROS-20019 Double strand breaks and cell-cycle arrest induced by the cyanobacterial toxin cylindrospermopsin in HepG2 cells The newly emerging cyanobacterial cytotoxin cylindrospermopsin (CYN) is increasingly found in surface freshwaters, worldwide. It poses a potential threat to humans after chronic exposure as it was shown to be genotoxic in a range of test systems and is potentially carcinogenic. However, the mechanisms of CYN toxicity and genotoxicity are not well understood. In the present study CYN induced formation of DNA double strand breaks (DSBs), after prolonged exposure (72 h), in human hepatoma cells, HepG2. CYN (0.1–0.5 µg/mL, 24–96 h) induced morphological changes and reduced cell viability in a dose and time dependent manner. No significant increase in lactate dehydrogenase (LDH) leakage could be observed after CYN exposure, indicating that the reduction in cell number was due to decreased cell proliferation and not due to cytotoxicity. This was confirmed by imunocytochemical analysis of the cell-proliferation marker Ki67. Analysis of the cell-cycle using flow-cytometry showed that CYN has an impact on the cell cycle, indicating G0/G1 arrest after 24 h and S-phase arrest after longer exposure (72 and 96 h). Our results provide new evidence that CYN is a direct acting genotoxin, causing DSBs, and these facts need to be considered in the human health risk assessment. cylindrospermopsin cell-cycle cell-proliferation double-strand breaks HepG2 cells true false true Angleški jezik Ni določen Neznano 2024-08-02 10:33:03 2024-08-02 10:33:03 2024-08-03 03:45:59 0000-00-00 00:00:00 2013 0 0 Nasl. z nasl. zaslona; Opis vira z dne 22. 8. 2013; str. 3077-3090 no. 8 Vol. 11 2013 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2013-08-21 577.1 1660-3397 10.3390/md11083077 2856527 http://www.mdpi.com/1660-3397/11/8/3077 1 1524b77f-5099-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27861 RAZ_Stern_Alja_2013.pdf RAZ_Stern_Alja_2013.pdf 1 DE924313682475169727514F5086DECC dfcd5a6ba8749fc8e7382321a2af5cba82f7d95865e8f81dbf2acf2d3c200829 6335234c-5099-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27862 https://doi.org/10.3390/md11083077 0 6c6d3db0-5099-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27863 Nacionalni inštitut za biologijo 0 0 0