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

Klara Hercog, Sara Maisanaba, Metka Filipič, Ángeles Jos, Ana M Cameán, Bojana Žegura
Author Information
  1. Klara Hercog: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Slovenia; Jozef Stefan International Postgraduate School, Ljubljana, Slovenia.
  2. Sara Maisanaba: Area of Toxicology, Department of Nutrition and Bromatology, Toxicology and Legal Medicine, Faculty of Pharmacy, University of Sevilla, Spain.
  3. Metka Filipič: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Slovenia.
  4. Ángeles Jos: Area of Toxicology, Department of Nutrition and Bromatology, Toxicology and Legal Medicine, Faculty of Pharmacy, University of Sevilla, Spain.
  5. Ana M Cameán: Area of Toxicology, Department of Nutrition and Bromatology, Toxicology and Legal Medicine, Faculty of Pharmacy, University of Sevilla, Spain.
  6. Bojana Žegura: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Slovenia. Electronic address: bojana.zegura@nib.si.

Abstract

Increased eutrophication of water bodies promotes cyanobacterial blooming that is hazardous due to the production of various bioactive compounds. Microcystin-LR (MCLR) is among the most widespread cyanotoxins classified as possible human carcinogen, while cylindrospermopsin (CYN) has only recently been recognized as health concern. Both cyanotoxins are genotoxic; however, the mechanisms of their action differ. They are ubiquitously present in water environment and are often detected together. Therefore, we studied genotoxic potential of the binary mixture of these cyanotoxins. Human hepatoma cells (HepG2) were exposed to a single dose of MCLR (1 μg/mL), graded doses of CYN (0.01-0.5 μg/mL), and their combinations. Comet and Cytokinesis block micronucleus assays were used to detect induction of DNA strand breaks (sb) and genomic instability, respectively, along with the transcriptional analyses of the expression of selected genes involved in xenobiotic metabolism, immediate/early cell response and DNA-damage response. MCLR induced DNA sb that were only transiently present after 4 h exposure, whereas CYN, after 24 h exposure, induced DNA sb and genomic instability. The MCLR/CYN mixture induced DNA sb after 24 h exposure, but to lesser extent as CYN alone. On the other hand, induction of genomic instability by the MCLR/CYN mixture was comparable to that induced by CYN alone. In addition, patterns of changes in the expression of selected genes induced by the MCLR/CYN mixture were not significantly different from those induced by CYN alone. Our results indicate that CYN exerts higher genotoxic potential than MCLR and that genotoxic potential of the MCLR/CYN mixture is comparable to that of CYN alone.

Keywords

MeSH Term

Alkaloids
Bacterial Toxins
Carcinogens
Carcinoma, Hepatocellular
Cyanobacteria
Cyanobacteria Toxins
DNA Damage
Eutrophication
Humans
Liver Neoplasms
Marine Toxins
Microcystins
Micronucleus Tests
Mutagenicity Tests
Uracil
Water Pollutants, Chemical

Chemicals

Alkaloids
Bacterial Toxins
Carcinogens
Cyanobacteria Toxins
Marine Toxins
Microcystins
Water Pollutants, Chemical
cylindrospermopsin
Uracil
cyanoginosin LR

Word Cloud

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