Cylindrospermopsin induces oxidative stress and genotoxic effects in the fish CLC cell line

J Appl Toxicol. 2015 Apr;35(4):426-33. doi: 10.1002/jat.3040. Epub 2014 Sep 12.

Abstract

Cylindrospermopsin (CYN) is a cyanotoxin detected in water reservoirs worldwide. The toxin is a potent protein synthesis inhibitor capable of adversely influencing a wide range of cell functions. While data on the prooxidative potency of CYN are inconsistent, genotoxic effects towards certain mammalian cell types have been described. However, such a potential on fish cells has not yet been investigated. Hence, the aim of the study was to elucidate the prooxidative and genotoxic impact of CYN on a common carp (Cyprinus carpio L.) leucocyte cell line (CLC). The cells were incubated with the cyanotoxin at concentrations of 0.1, 0.5 or 1 µg ml⁻¹. After 24 h, cytotoxic activity of CYN at the highest used concentration was confirmed by decreased cell membrane integrity and inhibited cell proliferation. Additionally, CYN at 0.5 and 1 µg ml⁻¹ increased intracellular ATP levels and decreased the reduced to oxidized glutathione ratio. Furthermore, a significant increase in the reactive oxygen species (ROS) production with concomitant changes in superoxide dismutase activity was observed after a 3.5-h exposure of the cells to the toxin. Genotoxic activity of CYN, manifested as oxidative DNA damage and elevated number of micronuclei, was also detected in exposed cells. The obtained results indicate that CYN is able to exert a wide range of adverse effects, including oxidative stress and genotoxicity in fish leucocytes.

Keywords: CLC cell line; cyanotoxin; cylindrospermopsin; genotoxicity; oxidative stress.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Alkaloids
  • Animals
  • Bacterial Toxins
  • Carps*
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Proliferation / drug effects
  • Cyanobacteria Toxins
  • DNA Damage
  • Fish Proteins / metabolism
  • Glutathione / metabolism
  • Leukocytes / drug effects*
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Marine Toxins / toxicity*
  • Micronuclei, Chromosome-Defective / chemically induced*
  • Micronucleus Tests
  • Mutagens / toxicity*
  • Osmolar Concentration
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism
  • Uracil / analogs & derivatives*
  • Uracil / toxicity

Substances

  • Alkaloids
  • Bacterial Toxins
  • Cyanobacteria Toxins
  • Fish Proteins
  • Marine Toxins
  • Mutagens
  • Reactive Oxygen Species
  • cylindrospermopsin
  • Uracil
  • Adenosine Triphosphate
  • Superoxide Dismutase
  • Glutathione