The emerging Fusarium toxin enniatin B: In-vitro studies on its genotoxic potential and cytotoxicity in V79 cells in relation to other mycotoxins

被引:28
作者
Föllmann W. [1 ]
Behm C. [1 ]
Degen G.H. [1 ]
机构
[1] Leibniz-Institut für Arbeitsforschung An der TU Dortmund (IfADo), Leibniz Research Centre for Working Environment and Human Factors, 44139 Dortmund
关键词
Cytotoxicity; Enniatin B; Fusarium toxins; Genotoxicity assays;
D O I
10.1007/s12550-008-0002-y
中图分类号
学科分类号
摘要
The Fusarium metabolite enniatin B is now recognized as a frequent contaminant of grains used for human foods and animal feeds. Yet, so far very limited data are available on its toxicity and that of other emerging Fusarium mycotoxins (Jestoi M, 2008, Crit Rev Food Sci Nutr 48:21-49). Thus, the mutagenic/genotoxic potential of enniatin B was investigated in a battery of short-term tests, and its cytotoxicity compared with that of several other mycotoxins. No mutagenicity was detected in the Ames assay with four Salmonella typhimurium strains, and in the HPRT (hypoxanthine guanine phosphoribosyl transferase) assay with V79 cells, in either the presence or absence of an external metabolizing enzyme system (rat liver S9). For other types of genotoxicity, i.e., clastogenicity and chromosomal damage, studied in V79 cells by means of alkaline single-cell gel electrophoresis (Comet) assay and micronucleus assay, no significant genotoxic potential of enniatin B was revealed. However, the Fusarium metabolite exerts pronounced time- and concentration-dependent cytotoxic effects in V79 cells as determined by Alamar Blue reduction and by neutral red uptake assays. For instance, IC20 and IC50 values determined for enniatin B by neutral red assay for 48-h exposure are 1.5 μM and 4 μM. These values are higher than those of the more potent Fusarium toxin deoxynivalenol (IC20 0.7 μM, IC50 of 0.8 μM), but clearly lower than the IC values of several other mycotoxins tested in parallel. Their ranking of cytotoxicity in V79 cells was as follows: deoxynivalenol > enniatin B > patulin > ochratoxin A > zearalenone > citrinin. Moreover, enniatin B was found to induce nuclear fragmentation, a sign of apoptosis, already at low submicromolar concentrations. In summary, despite an apparent lack of mutagenic and genotoxic activity, enniatin B can cause pronounced cytotoxicity in mammalian cells, detectable at low micromolar concentrations. © 2008 Society for Mycotoxin Research and Springer.
引用
收藏
页码:11 / 19
页数:8
相关论文
共 40 条
[1]  
Babich H., Borenfreund E., Cytotoxicity of T-2 toxin and its metabolites determined with the neutral red cell viability assay, Appl Environm Microbiol, 57, pp. 2101-2103, (1991)
[2]  
Behm C., Degen G.H., Follmann W., The Fusarium toxin enniatin B exerts no genotoxic activity, but pronounced cytotoxicity in vitro, Mol Nutr Food Res, (2009)
[3]  
Bonacker D., Stoiber T., Bohm K.J., Unger E., Degen G.H., Thier R., Bolt H.M., Chromosomal genotoxicity of nitrobenzene and benzonitrile, Archives of Toxicology, 78, 1, pp. 49-57, (2004)
[4]  
Degen G.H., Gerber M.M., Hillebrand I., Follmann W., Untersuchungen zur genotoxizität von ochratoxin a in zellkulturen von schwein und schaf, Proceedings of the 17th Mykotoxin-Workshop, (1995)
[5]  
Dorn S., Bolt H.M., Thevis M., Diel P., Degen G.H., Induction of micronuclei in V79 cells by the anabolic steroids tetrahydrogestrinone and trenbolone, Arch Toxicol, 82, pp. 257-263, (2008)
[6]  
Dornetshuber R., Heffeter P., Kamyar M.-R., Peterbauer T., Berger W., Lemmens-Gruber R., Enniatin exerts p53-dependent cytostatic and p53-independent cytotoxic activities against human cancer cells, Chemical Research in Toxicology, 20, 3, pp. 465-473, (2007)
[7]  
Firakova S., Proksa B., Sturdikova M., Biosynthesis and biological activities of enniatins, Pharmazie, 62, pp. 563-568, (2007)
[8]  
Follmann W., Lucas S., Effects of the mycotoxin ochratoxin A in a bacterial and a mammalian in vitro mutagenicity test system, Archives of Toxicology, 77, 5, pp. 298-304, (2003)
[9]  
Follmann W., Degen G.H., Behm C., Induction of micronuclei by ochratoxin A is a sensitive parameter of its genotoxicity in cultures cells, Mycotoxin Res, 23, pp. 101-109, (2007)
[10]  
Fornelli F., Minervini F., Logrieco A., Cytotoxicity of fungal metabolites to lepidopteran (Spodoptera frugiperda) cell line (SF-9), Journal of Invertebrate Pathology, 85, 2, pp. 74-79, (2004)