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Aneuploidogenic and clastogenic potential of the mycotoxins citrinin and patulin
E Pfeiffer1, K Gross, M Metzler
1Institute of Food Chemistry, University of Karlsruhe, Germany.
Abstract:
The aneuploidogenic and clastogenic potentials of the mycotoxins citrinin (CIT) and patulin (PAT) were studied by determining inhibition of microtubule assembly under cell-free conditions and by measuring induction of mitotic arrest and micronuclei in cultured Chinese hamster V79 cells. Both CIT and PAT inhibited cell-free microtubule polymerization in a concentration-dependent manner. PAT, but not CIT, bound covalently to reactive thiol groups of microtubule proteins. At concentrations without gross cytotoxicity, mitotic arrest and CREST-positive micronuclei, i.e. micronuclei containing whole chromosomes/chromatids, were induced by CIT and PAT in V79 cells. The time course of micronucleus induction and positive CREST staining indicate the aneuploidogenic potential of CIT and PAT. CREST-negative micronuclei, i.e. micronuclei containing acentric chromosomal fragments, were induced by PAT but not by CIT, implying a clastogenic potential of PAT. The aneuploidogenic and clastogenic potential of PAT and the aneuploidogenic potential of CIT may well contribute to the putative carcinogenicity of these mycotoxins in long-term animal studies.
Insights
The mycotoxins citrinin (CIT) and patulin (PAT) can cause genetic damage. Both toxins induced aneuploidy, while patulin also showed clastogenic potential, suggesting possible carcinogenicity.
Area of Science:
- Toxicology
- Cell Biology
- Genetics
Background:
- Mycotoxins citrinin (CIT) and patulin (PAT) are contaminants with potential health risks.
- Understanding their genotoxic mechanisms is crucial for risk assessment.
Purpose of the Study:
- To investigate the aneuploidogenic and clastogenic potentials of CIT and PAT.
- To elucidate the underlying mechanisms of their genotoxicity.
Main Methods:
- Inhibition of cell-free microtubule assembly.
- Induction of mitotic arrest and micronuclei in Chinese hamster V79 cells.
- Analysis of CREST-positive and CREST-negative micronuclei.
Main Results:
- Both CIT and PAT inhibited microtubule polymerization in a dose-dependent manner.
- CIT and PAT induced mitotic arrest and aneuploidy (CREST-positive micronuclei).
- PAT induced clastogenicity (CREST-negative micronuclei), but CIT did not.
Conclusions:
- CIT and PAT exhibit aneuploidogenic potential, contributing to their suspected carcinogenicity.
- PAT possesses both aneuploidogenic and clastogenic properties.
- These findings highlight the genotoxic risks associated with CIT and PAT exposure.