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In Vitro Mutagenic and Genotoxic Assessment of a Mixture of the Cyanotoxins Microcystin-LR and Cylindrospermopsin

Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C/Profesor García González 2, 41012 Sevilla, Spain
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Toxins 2019, 11(6), 318; https://doi.org/10.3390/toxins11060318
Received: 10 April 2019 / Revised: 29 May 2019 / Accepted: 31 May 2019 / Published: 4 June 2019
(This article belongs to the Special Issue Cyanobacteria and Cyanotoxins: New Advances and Future Challenges)
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Abstract

The co-occurrence of various cyanobacterial toxins can potentially induce toxic effects different than those observed for single cyanotoxins, as interaction phenomena cannot be discarded. Moreover, mixtures are a more probable exposure scenario. However, toxicological information on the topic is still scarce. Taking into account the important role of mutagenicity and genotoxicity in the risk evaluation framework, the objective of this study was to assess the mutagenic and genotoxic potential of mixtures of two of the most relevant cyanotoxins, Microcystin-LR (MC-LR) and Cylindrospermopsin (CYN), using the battery of in vitro tests recommended by the European Food Safety Authority (EFSA) for food contaminants. Mixtures of 1:10 CYN/MC-LR (CYN concentration in the range 0.04–2.5 µg/mL) were used to perform the bacterial reverse-mutation assay (Ames test) in Salmonella typhimurium, the mammalian cell micronucleus (MN) test and the mouse lymphoma thymidine-kinase assay (MLA) on L5178YTk± cells, while Caco-2 cells were used for the standard and enzyme-modified comet assays. The exposure periods ranged between 4 and 72 h depending on the assay. The genotoxicity of the mixture was observed only in the MN test with S9 metabolic fraction, similar to the results previously reported for CYN individually. These results indicate that cyanobacterial mixtures require a specific (geno)toxicity evaluation as their effects cannot be extrapolated from those of the individual cyanotoxins. View Full-Text
Keywords: genotoxicity; mutagenicity; Cylindrospermopsin; Microcystin-LR; mixture genotoxicity; mutagenicity; Cylindrospermopsin; Microcystin-LR; mixture
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Díez-Quijada, L.; Prieto, A.I.; Puerto, M.; Jos, Á.; Cameán, A.M. In Vitro Mutagenic and Genotoxic Assessment of a Mixture of the Cyanotoxins Microcystin-LR and Cylindrospermopsin. Toxins 2019, 11, 318.

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