Cyanobacterial Toxins: Genotoxic and Cytotoxic Activity, Molecular Targets and Chemical Interactions

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Marine and Freshwater Toxins".

Deadline for manuscript submissions: closed (1 September 2022) | Viewed by 10199

Special Issue Editors

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000 Ljubljana, Slovenia
Interests: cyanobacterial toxins; genetic toxicology; in vitro; advanced 3D cell models; toxicogenomics; ecotoxicology; combined exposures
Special Issues, Collections and Topics in MDPI journals
Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000 Ljubljana, Slovenia
Interests: genetic toxicology; epigenetic alternations; ecotoxicology; cyanotoxins; advanced model systems in genetic toxicology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Cyanobacteria are becoming a global environmental and human health problem as cyanobacterial blooms are increasing in frequency and magnitude worldwide, due to progressive eutrophication of water bodies and climate change. They produce a wide range of bioactive compounds including highly toxic cyanotoxins. Concern about their potential adverse effects, particularly after chronic exposure to low doses has been raised as humans can be exposed to cyanotoxins over a significant portion of their life span, with children being at higher risk for illnesses development. The mechanisms behind the toxic effects of cyanotoxins differ according to their chemical structure and molecular targets. In order to set the appropriate safety measures for the protection of human and animal health, as well as the environment throughout, toxicological evaluation of the emerging cyanotoxins (e.g., microcystins, cylindrospermopsin, nodularins, microginins, BMAA, etc.) is urgently needed. This Special Issue will highlight research on the cellular and molecular mechanisms behind the geno/toxic activity of cyanotoxins in the form of pure compounds and complex mixtures of several cyanotoxins. Moreover, papers describing novel predictive biomarkers of cyanotoxin geno/toxic effects identified by traditional toxicological approaches correlated to ‘omics‘ data are welcome.

Dr. Bojana Žegura
Dr. Alja Štern
Guest Editors

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Keywords

  • Emerging cyanotoxins
  • toxicity
  • genotoxicity
  • mechanisms of action
  • combined effects
  • risk assessment
  • molecular structure

Published Papers (4 papers)

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Research

13 pages, 1872 KiB  
Article
Target Mechanisms of the Cyanotoxin Cylindrospermopsin in Immortalized Human Airway Epithelial Cells
by Sabine Ziesemer, Susann Meyer, Julia Edelmann, Janita Vennmann, Celine Gudra, Denise Arndt, Marcus Effenberg, Olla Hayas, Aref Hayas, Johanna Sophia Thomassen, Barbara Kubickova, Dierk-Christoph Pöther and Jan-Peter Hildebrandt
Toxins 2022, 14(11), 785; https://doi.org/10.3390/toxins14110785 - 11 Nov 2022
Cited by 1 | Viewed by 1539
Abstract
Cylindrospermopsin (CYN) is a cyanobacterial toxin that occurs in aquatic environments worldwide. It is known for its delayed effects in animals and humans such as inhibition of protein synthesis or genotoxicity. The molecular targets and the cell physiological mechanisms of CYN, however, are [...] Read more.
Cylindrospermopsin (CYN) is a cyanobacterial toxin that occurs in aquatic environments worldwide. It is known for its delayed effects in animals and humans such as inhibition of protein synthesis or genotoxicity. The molecular targets and the cell physiological mechanisms of CYN, however, are not well studied. As inhalation of CYN-containing aerosols has been identified as a relevant route of CYN uptake, we analyzed the effects of CYN on protein expression in cultures of immortalized human bronchial epithelial cells (16HBE14o) using a proteomic approach. Proteins whose expression levels were affected by CYN belonged to several functional clusters, mainly regulation of protein stability, cellular adhesion and integration in the extracellular matrix, cell proliferation, cell cycle regulation, and completion of cytokinesis. With a few exceptions of upregulated proteins (e.g., ITI inhibitor of serine endopeptidases and mRNA stabilizer PABPC1), CYN mediated the downregulation of many proteins. Among these, centrosomal protein 55 (CEP55) and osteonectin (SPARC) were significantly reduced in their abundance. Results of the detailed semi-quantitative Western blot analyses of SPARC, claudin-6, and CEP55 supported the findings from the proteomic study that epithelial cell adhesion, attenuation of cell proliferation, delayed completion of mitosis, as well as induction of genomic instability are major effects of CYN in eukaryotic cells. Full article
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20 pages, 2054 KiB  
Article
Changes in Growth, Photosynthesis Performance, Pigments, and Toxin Contents of Bloom-Forming Cyanobacteria after Exposure to Macroalgal Allelochemicals
by Gracjana Budzałek, Sylwia Śliwińska-Wilczewska, Marek Klin, Kinga Wiśniewska, Adam Latała and Józef Maria Wiktor
Toxins 2021, 13(8), 589; https://doi.org/10.3390/toxins13080589 - 23 Aug 2021
Viewed by 2837
Abstract
Macroalgae can directly restrict the growth of various phytoplankton species by releasing allelopathic compounds; therefore, considerable attention should be paid to the allelopathic potential of these organisms against harmful and bloom-forming cyanobacteria. The main aim of this study was to demonstrate for the [...] Read more.
Macroalgae can directly restrict the growth of various phytoplankton species by releasing allelopathic compounds; therefore, considerable attention should be paid to the allelopathic potential of these organisms against harmful and bloom-forming cyanobacteria. The main aim of this study was to demonstrate for the first time the allelopathic activity of Ulva intestinalis on the growth, the fluorescence parameters: the maximum PSII quantum efficiency (Fv/Fm) and the effective quantum yield of PSII photochemistry (ΦPSII), the chlorophyll a (Chl a) and carotenoid (Car) content, and the microcystin-LR (MC-LR) and phenol content of three bloom-forming cyanobacteria, Aphanizomenon sp., Nodularia spumigena, and Nostoc sp. We found both negative and positive allelopathic effects of U. intestinalis on tested cyanobacteria. The study clearly showed that the addition of the filtrate of U. intestinalis significantly inhibited growth, decreased pigment content and Fv/Fm and ΦPSII values of N. spumigena and Nostoc sp., and stimulated Aphanizomenon sp. The addition of different concentrations of aqueous extract also stimulated the cyanobacterial growth. It was also shown that the addition of extract obtained from U. intestinalis caused a significant decrease in the MC-LR content in Nostoc sp. cells. Moreover, it the phenol content in N. spumigena cells was increased. On the other hand, the cell-specific phenol content for Aphanizomenon sp. decreased due to the addition of the filtrate. In this work, we demonstrated that the allelopathic effect of U. intestinalis depends on the target species’ identity as well as the type of allelopathic method used. The study of the allelopathic Baltic macroalgae may help to identify their possible role as a significant biological factor influencing harmful cyanobacterial blooms in brackish ecosystems. Full article
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15 pages, 1608 KiB  
Article
Cytotoxic and Genotoxic Effects of Cyanobacterial and Algal Extracts—Microcystin and Retinoic Acid Content
by Michal Bittner, Alja Štern, Marie Smutná, Klára Hilscherová and Bojana Žegura
Toxins 2021, 13(2), 107; https://doi.org/10.3390/toxins13020107 - 02 Feb 2021
Cited by 15 | Viewed by 2976
Abstract
In the last decade, it has become evident that complex mixtures of cyanobacterial bioactive substances, simultaneously present in blooms, often exert adverse effects that are different from those of pure cyanotoxins, and awareness has been raised on the importance of studying complex mixtures [...] Read more.
In the last decade, it has become evident that complex mixtures of cyanobacterial bioactive substances, simultaneously present in blooms, often exert adverse effects that are different from those of pure cyanotoxins, and awareness has been raised on the importance of studying complex mixtures and chemical interactions. We aimed to investigate cytotoxic and genotoxic effects of complex extracts from laboratory cultures of cyanobacterial species from different orders (Cylindrospermopsis raciborskii, Aphanizomenon gracile, Microcystis aeruginosa, M. viridis, M. ichtyoblabe, Planktothrix agardhii, Limnothrix redekei) and algae (Desmodesmus quadricauda), and examine possible relationships between the observed effects and toxin and retinoic acid (RA) content in the extracts. The cytotoxic and genotoxic effects of the extracts were studied in the human hepatocellular carcinoma HepG2 cell line, using the MTT assay, and the comet and cytokinesis-block micronucleus (cytome) assays, respectively. Liquid chromatography electrospray ionization mass spectrometry (LC/ESI-MS) was used to detect toxins (microcystins (MC-LR, MC-RR, MC-YR) and cylindrospermopsin) and RAs (ATRA and 9cis-RA) in the extracts. Six out of eight extracts were cytotoxic (0.04–2 mgDM/mL), and five induced DNA strand breaks at non-cytotoxic concentrations (0.2–2 mgDM/mL). The extracts with genotoxic activity also had the highest content of RAs and there was a linear association between RA content and genotoxicity, indicating their possible involvement; however further research is needed to identify and confirm the compounds involved and to elucidate possible genotoxic effects of RAs. Full article
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16 pages, 1630 KiB  
Article
Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
by Leticia Díez-Quijada, Klara Hercog, Martina Štampar, Metka Filipič, Ana M. Cameán, Ángeles Jos and Bojana Žegura
Toxins 2020, 12(12), 778; https://doi.org/10.3390/toxins12120778 - 08 Dec 2020
Cited by 13 | Viewed by 2132
Abstract
Simultaneous occurrence of cylindrospermopsin (CYN) and microcystin-LR (MCLR) has been reported in the aquatic environment and thus human exposure to such mixtures is possible. As data on the combined effects of CYN/MCLR are scarce, we aimed to investigate the adverse effects related to [...] Read more.
Simultaneous occurrence of cylindrospermopsin (CYN) and microcystin-LR (MCLR) has been reported in the aquatic environment and thus human exposure to such mixtures is possible. As data on the combined effects of CYN/MCLR are scarce, we aimed to investigate the adverse effects related to genotoxic activities induced by CYN (0.125, 0.25 and 0.5 µg/mL) and MCLR (1 µg/mL) as single compounds and their combinations in HepG2 cells after 24 and 72 h exposure. CYN and CYN/MCLR induced DNA double-strand breaks after 72 h exposure, while cell cycle analysis revealed that CYN and CYN/MCLR arrested HepG2 cells in G0/G1 phase. Moreover, CYN and the combination with MCLR upregulated CYP1A1 and target genes involved in DNA-damage response (CDKN1A, GADD45A). Altogether, the results showed that after 72 h exposure genotoxic activity of CYN/MCLR mixture was comparable to the one of pure CYN. On the contrary, MCLR (1 µg/mL) had no effect on the viability of cells and had no influence on cell division. It did not induce DNA damage and did not deregulate studied genes after prolonged exposure. The outcomes of the study confirm the importance of investigating the combined effects of several toxins as the effects can differ from those induced by single compounds. Full article
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