The Fusarium toxin enniatin B exerts no genotoxic activity, but pronounced cytotoxicity in vitro

Enniatin B, a fungal metabolite produced by various Fusarium strains, is a frequent contaminant in cereals used for human foods and animal feeds, but, so far very limited data are available oil its toxicity. The aim of this study was to investigate the effects of enniatin B in a battery of short-term tests to evaluate its genotoxic potential. In Salmonella typhimurium assays (Ames assay) with the strains TA 98, TA 100, TA 102, and TA 104, both in the presence and absence of an external metabolizing enzyme system (rat liver S9), no mutagenicity was detected up to toxic levels (100 mu M) of enniatin B. Likewise, mutagenicity tests in mammalian cells, i.e., the hypoxanthin-guanin-phosphoribosyl-transferase (HPRT) assay with V79 cells performed with and without S9 mix, did not reveal a significant increase in mutant frequency for enniatin B LIP to 30 mu M, a cytotoxic concentration. Additional tests oil other types of genotoxicity, i.e., clastogenicity and chromosomal damage, were conducted in V79 cells, applying the alkaline single cell gel electrophoresis (Comet assay with and without FPG, formamidopyramidine DNA glycosylase, enzyme) and the micronucleus assay. None of these assays revealed a significant genotoxic potential of enniatin B. However, enniatin B exerts pronounced cytotoxic effects in V79 cells as determined by neutral red uptake assay for 48 h exposure: The IC20 and IC50 values of 1.5 and 4 mu M, are higher than those of the more potent Fusarium toxin deoxynivalenol (IC20 0.6 mu M, IC50 of 0.8 mu M), but in I similar range as values reported for cytotoxicity of enniatin B in various tumor cell lines. In summary, despite an apparent lack of genotoxic activity, enniatin B call exert biological activity at low micromolar concentrations in mammalian cells.