Abstract
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.
Highlights
The cyanobacterial toxin cylindrospermopsin (CYN) is synthesized by a number of freshwater cyanobacterial species and is increasingly being recognized as a potential threat to drinking water safety, worldwide
It is generally accepted that CYN is genotoxic as it induces DNA damage in several in vitro [7,8,9,10,11,19]
In the present study the formation of DNA double strand breaks (DSBs) by CYN was shown for the first time
Summary
The cyanobacterial toxin cylindrospermopsin (CYN) is synthesized by a number of freshwater cyanobacterial species (for review see: [1]) and is increasingly being recognized as a potential threat to drinking water safety, worldwide. The toxin is a potent protein synthesis inhibitor [6], and contains several potential sites for reactivity that may form protein and DNA adducts. There is evidence for its genotoxic activity in vitro [7,8,9,10,11] and in vivo [12,13], and even carcinogenic potential of CYN has been indicated by preliminary results [14]. Despite of its apparent hazard, the mechanisms involved in CYN genotoxic and especially carcinogenic activity are poorly understood.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
