In vivo genotoxicity evaluation of cylindrospermopsin in rats using a combined micronucleus and comet assay

Food Chem Toxicol. 2019 Oct:132:110664. doi: 10.1016/j.fct.2019.110664. Epub 2019 Jul 3.

Abstract

Cylindrospermopsin (CYN) is a potent cyanotoxin recognized as an emerging human threat due to its cytotoxicity and potential carcinogenicity. Although the genotoxicity of CYN has been extensively studied in vitro, limited data are available on its in vivo genotoxicity. The aim of this study was to evaluate the in vivo genotoxicity of pure CYN (7.5-75 μg/kg body weight) after oral exposure of rats through a combined assay of the micronucleus test (MN) in bone marrow, and the standard and modified comet assay in stomach, liver and blood. Also, histopathological changes in stomach and liver were evaluated. Positive results in the MN test were observed in bone marrow in the exposed rats at all the tested concentrations. However, the comet assay revealed that CYN did not induce DNA strand breaks nor oxidative DNA damage in any of the tissues investigated. Finally, histopathological changes were observed in stomach and liver (7.5-75 μg/kg) in intoxicated rats. These results could indicate that CYN is able to induce irritation in stomach before its biotransformation in rats orally exposed, and genotoxicity in bone marrow.

Keywords: Comet assay; Cylindrospermopsin; Genotoxicity; Micronucleus; Oxidative DNA damage; Rats.

MeSH terms

  • Alkaloids
  • Animals
  • Bacterial Toxins / toxicity*
  • Bone Marrow / drug effects
  • Comet Assay*
  • Cyanobacteria Toxins
  • DNA Damage
  • Liver / drug effects
  • Male
  • Micronucleus Tests*
  • Mutagens / toxicity*
  • Rats
  • Rats, Wistar
  • Stomach / drug effects
  • Uracil / analogs & derivatives*
  • Uracil / toxicity

Substances

  • Alkaloids
  • Bacterial Toxins
  • Cyanobacteria Toxins
  • Mutagens
  • cylindrospermopsin
  • Uracil