Cell alterations but no DNA strand breaks induced in vitro by cylindrospermopsin in CHO K1 cells

Environ Toxicol. 2003 Oct;18(5):353-9. doi: 10.1002/tox.10136.

Abstract

Cylindrospermopsin has been involved in some cyanobacterial blooms associated with animal and human intoxications in different countries. Liver is the main target organ even though thymus and kidney are also affected. Its toxic effect has been shown to be induced by protein synthesis inhibition. However, further research about its toxicological potential is required, as revealed by the U.S. Unregulated Contaminant Monitoring Regulation (US UCMR) meeting in 2001. Induction of DNA damage by cylindrospermopsin has been reported by some authors either by a direct effect on DNA or by an indirect effect on associated macromolecules. This study focused on evaluating its in vitro genotoxic potential using the comet assay coupled to various cell alteration measurements. No DNA damage was detected by the alkaline comet assay on Chinese hamster ovary (CHO) K1 cells after 24 h of treatment with cylindrospermopsin concentrations of 0.5 and 1 microg mL(-1). However, inhibition of cell growth was noticed as well as cell blebbing and rounding. These morphological effects were linked to cytoskeletal reorganization (mainly microfilaments) but not to apoptosis. This study concluded that cylindrospermopsin does not obviously react directly with DNA in CHO K1 cells. But the hypothesis of its metabolization into a genotoxic product must be explored further.

MeSH terms

  • Alkaloids
  • Animals
  • Bacterial Toxins
  • CHO Cells
  • Comet Assay
  • Cricetinae
  • Cricetulus
  • Cyanobacteria
  • Cyanobacteria Toxins
  • Cytoskeleton / drug effects
  • Cytoskeleton / pathology*
  • DNA Damage*
  • Dose-Response Relationship, Drug
  • Uracil / analogs & derivatives*
  • Uracil / toxicity*

Substances

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