Genotoxic potential of the binary mixture of cyanotoxins microcystin-LR and cylindrospermopsin

Cytotoxic and morphological effects of microcystin‐LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2

“…Regarding to MC‐LR, there are several studies in the scientific literature in HepG2 cells but most of them used lower concentrations than in the present work as they were focused on the study of toxicity mechanisms and not in deriving EC 50 values (ie, Refs. ). Chong et al concluded that MC‐LR did not cause cytotoxic effects in HepG2 cells and other hepatic cell line in 48–96 h of exposure to concentrations up to 100 μg/mL.…”

“…Literature concerning cyanotoxin interactions is very scarce according to the scientific report for the EFSA carried out by Testai et al As far as we know, there is only an in vitro study that evaluated the effects of CYN/MC‐LR combinations on the HepG2 cell line, but it was related to their genotoxic potential. Thus, Hercog et al first performed a cytotoxicity test (MTS assay) in cells treated with CYN (0.01, 0.05, 0.1, and 0.5 μg/mL), MC‐LR (1.0 μg/mL) and their combinations for 4 and 24 h. In cells exposed to MC‐LR (1 μg/mL) in combination with CYN (0.5 μg/mL) the viability was decreased to 80% compared to solvent control. They observed that the MC‐LR/CYN combination induced DNA strand breaks after 24 h exposure, but to a lesser extent as CYN alone.…”

“…Its mechanism of action stands out by the inhibition of protein synthesis and glutathione (GSH) synthesis . Moreover, cytotoxity, oxidative stress, mutagenicity, and genotoxicity have been also elucidated as toxic mechanisms of CYN . These two cyanotoxins have been widely studied separately, but little is known about their effects when they are combined.…”

“…It has been described some cyanobacterial strains are able to produce different cyanotoxins or different congeners of a cyanotoxin . There are several studies concerning the co‐occurrence of MCs‐ and CYN‐producing cyanobacteria as well as the presence of combinations of both cyanotoxins at the same time . In this sense, Graham et al found that MCs are the most abundant cyanotoxins in blooms from USA, being present in all of them.…”

“…The little research published so far on the toxic effects of MCs/CYN combinations is mainly focused on plants . However, Hercog et al evaluated in vitro the genotoxic potential of the each toxin alone and their combination on HepG2 cells, concluding that MC‐LR did not show a role on the deregulation of the genes investigated, attributing all the effect to CYN. Although these authors did not perform an isobologram analysis to determine the type of interaction observed”.…”