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Published on: September 5, 2017
Cell alterations but no DNA strand breaks induced in vitro by cylindrospermopsin in CHO K1 cells
Valérie Fessard1, Cécile Bernard
1Agence Française de Sécurité Sanitaire des Aliments, Unité de Toxicologie Alimentaire, BP 90 203, 35 302 Fougères, France. v.fessard@fougeres.afssa.fr
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.
Insights
Cylindrospermopsin, a cyanobacterial toxin, did not directly damage DNA in Chinese hamster ovary cells. However, it inhibited cell growth and caused morphological changes, suggesting potential indirect genotoxicity requiring further investigation.
Area of Science:
- Environmental toxicology
- Cell biology
- Genotoxicity testing
Background:
- Cylindrospermopsin is a cyanotoxin linked to animal and human intoxications.
- The liver is the primary target organ, but thymus and kidney can also be affected.
- Protein synthesis inhibition underlies its toxic effects, with ongoing research into its full toxicological potential.
Purpose of the Study:
- To evaluate the in vitro genotoxic potential of cylindrospermopsin.
- To investigate cylindrospermopsin's effects on DNA integrity and cellular alterations.
- To assess direct DNA damage and indirect effects using the comet assay and cell-based measurements.
Main Methods:
- Utilized the alkaline comet assay to detect DNA damage in Chinese hamster ovary (CHO) K1 cells.
- Treated cells with cylindrospermopsin at concentrations of 0.5 and 1 microg mL(-1) for 24 hours.
- Monitored cell growth inhibition, morphological changes (blebbing, rounding), and apoptosis.
Main Results:
- No direct DNA damage was observed using the alkaline comet assay.
- Significant inhibition of cell growth was detected.
- Morphological alterations, including cell blebbing and rounding, were observed, linked to cytoskeletal reorganization, not apoptosis.
Conclusions:
- Cylindrospermopsin does not appear to directly interact with DNA in CHO K1 cells under the tested conditions.
- Observed cellular effects suggest potential indirect genotoxicity, possibly through metabolization into a genotoxic compound.
- Further research is warranted to explore the metabolization pathways and genotoxic potential of cylindrospermopsin.
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